Abstract
The mast cells are multi-effector cells with wide distribution in the different body parts and traditionally their role has been well-defined in the development of IgE-mediated hypersensitivity reactions including bronchial asthma. Due to the availability of genetically modified mast cell-deficient mice, the broadened pathophysiological role of mast cells in diverse diseases has been revealed. Mast cells exert different physiological and pathophysiological roles by secreting their granular contents, including vasoactive amines, cytokines and chemokines, and various proteases, including tryptase and chymase. Furthermore, mast cells also synthesize plasma membrane-derived lipid mediators, including prostaglandins and leukotrienes, to produce diverse biological actions. The present review discusses the pathophysiological role of mast cells in different diseases, including atherosclerosis, pulmonary hypertension, ischemia-reperfusion injury, male infertility, autoimmune disorders such as rheumatoid arthritis and multiple sclerosis, bladder pain syndrome (interstitial cystitis), anxiety, Alzheimer’s disease, nociception, obesity and diabetes mellitus.
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Adam M, Schwarzer JU, Köhn FM, Strauss L, Poutanen M, Mayerhofer A (2011) Mast cell tryptase stimulates production of decorin by human testicular peritubular cells: possible role of decorin in male infertility by interfering with growth factor signaling. Hum Reprod 26:2613–2625
Addolorato G, Marsigli L, Capristo E, Caputo F, Dall’Aglio C, Baudanza P (1998) Anxiety and depression: a common feature of health care seeking patients with irritable bowel syndrome and food allergy. Hepatogastroenterology 45:1559–1564
Allam JP, Langer M, Fathy A, Oltermann I, Bieber T, Novak N, Haidl G (2009) Mast cells in the seminal plasma of infertile men as detected by flow cytometry. Andrologia 41:1–6
Alton EW, Norris AA (1996) Chloride transport and the actions of nedocromil sodium and cromolyn sodium in asthma. J Allergy Clin Immunol 98:S102–S105
Azadi L, Abbasi H, Deemeh MR, Tavalaee M, Arbabian M, Pilevarian AA, Nasr-Esfahani MH (2011) Zaditen (Ketotifen), as mast cell blocker, improves sperm quality, chromatin integrity and pregnancy rate after varicocelectomy. Int J Androl 34:446–452
Banasova A, Maxova H, Hampl V, Vizek M, Povysilova V, Novotna J, Vajnerova O, Hnilickova O, Herget J (2008) Prevention of mast cell degranulation by disodium cromoglycate attenuates the development of hypoxic pulmonary hypertension in rats exposed to chronic hypoxia. Respiration 76:102–107
Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini D, Pasquinelli G, Morselli-Labate AM, Grady EF, Bunnett NW, Collins SM, Corinaldesi R (2004) Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 126:693–702
Bartelds B, van Loon RL, Mohaupt S, Wijnberg H, Dickinson M, Boersma B, Takens J, van Albada M, Berger RM (2012) Mast cell inhibition improves pulmonary vascular remodeling in pulmonary hypertension. Chest 141:651–660
Bebo BF Jr, Lee CH, Orr EL, Linthicum DS (1996) Mast cell-derived histamine and tumour necrosis factor: differences between SJL/J and BALB/c inbred strains of mice. Immunol Cell Biol 74:225–230
Bennett JL, Blanchet MR, Zhao L, Zbytnuik L, Antignano F, Gold M, Kubes P, McNagny KM (2009) Bone marrow-derived mast cells accumulate in the central nervous system during inflammation but are dispensable for experimental autoimmune encephalomyelitis pathogenesis. J Immunol 182:5507–5514
Bian ZX, Li Z, Huang ZX, Zhang M, Chen HL, Xu HX, Sung JJ (2009) Unbalanced expression of protease-activated receptors-1 and −2 in the colon of diarrhea-predominant irritable bowel syndrome patients. J Gastroenterol 44:666–674
Bischoff SC, Dahinden CA (1992) c-Kit ligand: a unique potentiator of mediator release by human lung mast cells. J Exp Med 175:237–244
Bischoff SC, Wedemeyer J, Herrmann A, Meier PN, Trautwein C, Cetin Y, Maschek H, Stolte M, Gebel M, Manns MP (1996) Quantitative assessment of intestinal eosinophils and mast cells in inflammatory bowel disease. Histopathology 28:1–13
Bot I, Biessen EA (2011) Mast cells in atherosclerosis. Thromb Haemost 106:820–826
Bot I, de Jager SCA, Bot M, van Heiningen SH, de Groot P, Veldhuizen RW, van Berkel TJ, von der Thüsen JH, Biessen EA (2010) The neuropeptide substance P mediates adventitial mast cell activation and induces intraplaque hemorrhage in advanced atherosclerosis. Circ Res 106:89–92
Bot I, Bot M, van Heiningen SH, van Santbrink PJ, Lankhuizen IM, Hartman P, Gruener S, Hilpert H, van Berkel TJ, Fingerle J, Biessen EA (2011) Mast cell chymase inhibition reduces atherosclerotic plaque progression and improves plaque stability in ApoE−/− mice. Cardiovasc Res 89:244–252
Boucher W, el-Mansoury M, Pang X, Sant GR, Theoharides TC (1995) Elevated mast cell tryptase in the urine of patients with interstitial cystitis. Br J Urol 76:94–100
Ch’ng S, Wallis RA, Yuan L, Davis PF, Tan ST (2006) Mast cells and cutaneous malignancies. Mod Pathol 19:149–159
Chang DZ, Ma Y, Ji B, Wang H, Deng D, Liu Y, Abbruzzese JL, Liu Y, Logsdon CD, Hwu P (2011) Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma. Clin Cancer Res 17:7015–7023
Chen R, Ning G, Zhao ML, Fleming MG, Diaz LA, Werb Z, Liu Z (2001) Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid. J Clin Invest 108:1151–1158
Clejan S, Japa S, Clemetson C, Hasabnis SS, David O, Talano JV (2002) Blood histamine is associated with coronary artery disease, cardiac events and severity of inflammation and atherosclerosis. J Cell Mol Med 6:583–592
Couturier N, Zappulla JP, Lauwers-Cances V, Uro-Coste E, Delisle MB, Clanet M, Montagne L, Van der Valk P, Bö L, Liblau RS (2008) Mast cell transcripts are increased within and outside multiple sclerosis lesions. J Neuroimmunol 195:176–185
Cremon C, Carini G, Wang B, Vasina V, Cogliandro RF, De Giorgio R, Stanghellini V, Grundy D, Tonini M, De Ponti F, Corinaldesi R, Barbara G (2011) Intestinal serotonin release, sensory neuron activation, and abdominal pain in irritable bowel syndrome. Am J Gastroenterol 106:1290–1298
Czyzewska-Buczyńska A, Witkiewicz W (2011) Role of mast cells in the pathogenesis of atherosclerosis. Przegl Lek 68:171–174
Dahal BK, Kosanovic D, Kaulen C, Cornitescu T, Savai R, Hoffmann J, Reiss I, Ghofrani HA, Weissmann N, Kuebler WM, Seeger W, Grimminger F, Schermuly RT (2011) Involvement of mast cells in monocrotaline-induced pulmonary hypertension in rats. Respir Res 12:60
De Filippis D, Luongo L, Cipriano M, Palazzo E, Cinelli MP, de Novellis V, Maione S, Iuvone T (2011) Palmitoylethanolamide reduces granuloma-induced hyperalgesia by modulation of mast cell activation in rats. Mol Pain 7:3
Donoso AO, Broitman ST (1979) Effects of a histamine synthesis inhibitor and antihistamines on the sexual behavior of female rats. Psychopharmacology (Berl) 66:251–255
Dunn AJ (2000) Cytokine activation of the HPA axis. Ann N Y Acad Sci 917:608–617
El-Karaksy A, Mostafa T, Shaeer OK, Bahgat DR, Samir N (2007) Seminal mast cells in infertile asthenozoospermic males. Andrologia 39:244–247
el-Mansoury M, Boucher W, Sant GR, Theoharides TC (1994) Increased urine histamine and methylhistamine in interstitial cystitis. J Urol 152:350–353
Erickson DR, Belchis DA, Dabbs DJ (1997) Inflammatory cell types and clinical features of interstitial cystitis. J Urol 158:790–793
Frangogiannis NG, Perrard JL, Mendoza LH, Burns AR, Lindsey ML, Ballantyne CM, Michael LH, Smith CW, Entman ML (1998) Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischaemia and reperfusion. Circulation 98:687–698
Frangogiannis NG, Smith CW, Entman ML (2002) The inflammatory response in myocardial infarction. Cardiovasc Res 53:31–47
Frieling T, Meis K, Kolck UW, Homann J, Hülsdonk A, Haars U, Hertfelder HJ, Oldenburg J, Seidel H, Molderings GJ (2011) Evidence for mast cell activation in patients with therapy-resistant irritable bowel syndrome. Z Gastroenterol 49:191–194
Galli SJ (1990) New insights into the riddle of the mast cells: microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab Invest 62:5–33
Galli SJ, Tsai M (2010) Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity. Eur J Immunol 40:1843–1851
Gambaryan N, Perros F, Montani D, Cohen-Kaminsky S, Mazmanian GM, Humbert M (2010) Imatinib inhibits bone marrow-derived c-kit+ cell mobilisation in hypoxic pulmonary hypertension. Eur Respir J 36:1209–1211
Gambaryan N, Perros F, Montani D et al (2011) Targeting of c-kit+ hematopoietic progenitor cells prevents hypoxic pulmonary hypertension. Eur Respir J 37:1392–1399
Gandhi R, Laroni A, Weiner HL (2010) Role of the innate immune system in the pathogenesis of multiple sclerosis. J Neuroimmunol 221:7–14
Gao G, Ouyang A, Kaufman MP, Yu S (2011) ERK1/2 signaling pathway in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons. Dis Esophagus 24:194–203
Goral V, Kucukoner M, Buyukbayram H (2010) Mast cells count and serum cytokine levels in patients with irritable bowel syndrome. Hepatogastroenterology 57:751–754
Guma M, Kashiwakura J, Crain B, Kawakami Y, Beutler B, Firestein GS, Kawakami T, Karin M, Corr M (2010) JNK1 controls mast cell degranulation and IL-1{beta} production in inflammatory arthritis. Proc Natl Acad Sci USA 107:22122–22127
Guo T, Chen WQ, Zhang C, Zhao YX, Zhang Y (2009) Chymase activity is closely related with plaque vulnerability in a hamster model of atherosclerosis. Atherosclerosis 207:59–67
Haidl G, Duan YG, Chen SJ, Kohn FM, Schuppe HC, Allam JP (2011) The role of mast cells in male infertility. Expert Rev Clin Immunol 7:627–634
Hamada H, Terai M, Kimura H, Hirano K, Oana S, Niimi H (1999) Increased expression of mast cell chymase in the lungs of patients with congenital heart disease associated with early pulmonary vascular disease. Am J Respir Crit Care Med 160:1303–1308
Hassoun PM, Mouthon L, Barber JA, Eddahibi S, Flores SC, Grimminger F, Jones PL, Maitland ML, Michelakis ED, Morrell NW, Newman JH, Rabinovitch M, Schermuly R, Stenmark KR, Voelkel NF, Yuan JXJ, Humbert M (2009) Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol 54:S10–S19
Hauer AD, de Vos P, Peterse N et al (2006) Delivery of Chlamydia pneumoniae to the vessel wall aggravates atherosclerosis in LDLr−/− mice. Cardiovasc Res 69:280–288
Heath D, Yacoub M (1991) Lung mast cells in plexogenic pulmonary arteriopathy. J Clin Pathol 44:1003–1006
Hegyesi H, Somlai B, Varga VL (2001) Suppression of melanoma cell proliferation by histidine decarboxylase specific antisense oligonucleotides. J Invest Dermatol 117:151–153
Hei ZQ, Gan XL, Huang PJ, Wei J, Shen N, Gao WL (2008) Influence of Ketotifen, Cromolyn Sodium, and Compound 48/80 on the survival rates after intestinal ischemia reperfusion injury in rats. BMC Gastroenterol 8:42
Hendrix S, Warnke K, Siebenhaar F, Peters EM, Nitsch R, Maurer M (2006) The majority of brain mast cells in B10.PL mice is present in the hippocampal formation. Neurosci Lett 392:174–177
Hibi H, Kato K, Mitsui K, Taki T, Yamada Y, Honda N, Fukatsu H, Yamamoto M (2002) Treatment of oligoasthenozoospermia with tranilast, a mast cell blocker, after long-term administration. Arch Androl 48:451–459
Hoffmann J, Yin J, Kukucka M, Yin N, Saarikko I, Sterner-Kock A, Fujii H, Leong-Poi H, Kuppe H, Schermuly RT, Kuebler WM (2011) Mast cells promote lung vascular remodelling in pulmonary hypertension. Eur Respir J 37:1400–1410
Hueber AJ, Asquith DL, Miller AM, Reilly J, Kerr S, Leipe J, Melendez AJ, McInnes IB (2010) Mast cells express IL-17A in rheumatoid arthritis synovium. J Immunol 184:3336–3340
Ikarashi Y, Yuzurihara M (2002) Experimental anxiety induced by histaminergics in mast cell-deficient and congenitally normal mice. Pharmacol Biochem Behav 72:437–441
Imada D, Shijubo N, Kojima H, Abe S (2000) Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma. Eur Respir J 15:1087–1093
Ito A, Jippo T, Wakayama T, Morii E, Koma Y, Onda H, Nojima H, Iseki S, Kitamura Y (2003) SgIGSF: a new mast-cell adhesion molecule used for attachment to fibroblasts and transcriptionally regulated by MITF. Blood 101:2601–2608
Jaggi AS, Singh M, Sharma A, Singh D, Singh N (2007) Cardioprotective effects of mast cell modulators in ischemia-reperfusion-induced injury in rats. Methods Find Exp Clin Pharmacol 29:593–600
Jakate S, Demeo M, John R, Tobin M, Keshavarzian A (2006) Mastocytic enterocolitis: increased mucosal mast cells in chronic intractable diarrhea. Arch Pathol Lab Med 130:362–367
Jeziorska M, McCollum C, Woolley DE (1997) Mast cell distribution, activation, and phenotype in atherosclerotic lesions of human carotid arteries. J Pathol 182:115–122
Johnson D, Krenger W (1992) Interactions of mast cells with the nervous system—recent advances. Neurochem Res 17:939–951
Johnson D, Yasui D, Seeldrayers P (1991) An analysis of mast cell frequency in the rodent nervous system: numbers vary between different strains and can be reconstituted in mast cell-deficient mice. J Neuropathol Exp Neurol 50:227–234
Jolly SR, Abrams GD, Romson JL, Bailie MB, Lucchesi BR (1982) Effects of lodoxamide on ischaemic reperfused myocardium. J Cardiovasc Pharmacol 4:441–448
Kaartinen M, Pentillä A, Kovanen PT (1994) Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation 90:1669–1678
Kaartinen M, Pentillä A, Kovanen PT (1996) Mast cells accompany microvessels in human coronary atheromas: implications for intimal neovascularization and hemorrhage. Atherosclerosis 123:123–131
Kakizoe E, Li SH, Kobayashi Y, Nishikori Y, Dekio S, Okunishi H (1999) Increases in mast cells and chymase in fibroproliferative paws of collagen-induced arthritic mice. Inflamm Res 48:318–324
Keller AM, Clancy RM, Barr ML, Marboe CC, Cannon PJ (1988) Acute reoxygenation injury in the isolated rat heart: role of resident cardiac mast cells. Circ Res 63:1044–1052
Kelley J, Hemontolor G, Younis W (2006) Mast cell activation by lipoproteins. Methods Mol Biol 315:341–348
Kim DY, Jeoung D, Ro JY (2010) Signaling pathways in the activation of mast cells cocultured with astrocytes and colocalization of both cells in experimental allergic encephalomyelitis. J Immunol 185:273–283
Kitamura Y, Go S, Hatanaka K (1978) Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood 52:447–452
Klooker TK, Braak B, Koopman KE, Welting O, Wouters MM, van der Heide S, Schemann M, Bischoff SC, van den Wijngaard RM, Boeckxstaens GE (2010) The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut 59:1213–1221
Kokkonen JO, Kovanen PT (1987a) Low-density-lipoprotein binding by mast-cell granules. Demonstration of binding of apolipoprotein B to heparin proteoglycan of exocytosed granules. Biochem J 241:583–589
Kokkonen JO, Kovanen PT (1987b) Stimulation of mast cells leads to cholesterol accumulation in macrophages in vitro by a mast cell granule-mediated uptake of low density lipoprotein. Proc Natl Acad Sci USA 84:2287–2291
Kondo S, Kagami S, Kido H, Strutz F, Müller GA, Kuroda Y (2001) Role of mast cell tryptase in renal interstitial fibrosis. J Am Soc Nephrol 12:1668–1676
Kormelink TG, Abudukelimu A, Redegeld FA (2009) Mast cells as target in cancer therapy. Curr Pharm Des 15:1868–1878
Kovács P, Hernádi I, Wilhelm M (2006) Mast cells modulate maintained neuronal activity in the thalamus in vivo. J Neuroimmunol 171:1–7
Kovanen PT, Kaartinen M, Paavonen T (1995) Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. Circulation 92:1084–1088
Kovanen PT, Mänttäri M, Palosuo T, Manninen V, Aho K (1998) Prediction of myocardial infarction in dyslipidemic men by elevated levels of immunoglobulin classes A, E, and G, but not M. Arch Intern Med 158:1434–1439
Kubes P, Granger DN (1996) Leukocyte-endothelial cell interactions evoked by mast cells. Cardiovasc Res 32:699–708
Kvetnoĭ IM, Kvetnaia TV, Riadnova IIu, Fursov BB, Ernandes-Jago H, Blesa JR (2003) Expression of beta-amyloid and tau-protein in mastocytes in Alzheimer disease. Arkh Patol 65:36–39
Laine P, Naukkarinen A, Heikkilä L, Penttilä A, Kovanen PT (2000) Adventitial mast cells connect with sensory nerve fibers in atherosclerotic coronary arteries. Circulation 101:1665–1669
Lampiasi N, Azzolina A, Montalto G, Cervello M (2007) Histamine and spontaneously released mast cells granules affect the cell growth of human hepatocellular carcinoma cells. Exp Mol Med 39:284–294
Lappalainen H, Laine P, Pentikäinen MO et al (2004) Mast cells in neovascularized human coronary plaques store and secrete basic fibroblast growth factor, a potent angiogenic mediator. Arterioscler Thromb Vasc Biol 24:1880–1885
Le Filliatre G, Sayah S, Latournerie V, Renaud JF, Finet M, Hanf R (2001) Cyclooxygenase and lipoxygenase pathways in mast cell dependent neurogenic inflammation induced by electrical stimulation of the rat saphenous nerve. Br J Pharmacol 132:1581–1589
Lee T (2011) New insights into the mechanism of the down-regulation of mast cells in the treatment of interstitial cystitis: possible role of siglecs. Int Neurourol J 15:59–60
Lee DM, Friend DS, Gurish MF, Benoist C, Mathis D, Brenner MB (2002) Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 297:1689–1692
Lehrer PM, Isenberg S, Hochron SM (1993) Asthma and emotion: a review. J Asthma 30:5–21
Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM (2007) Mast cell degranulation activates a pain pathway underlying migraine headache. Pain 130:166–176
Li H, Nourbakhsh B, Safavi F, Li K, Xu H, Cullimore M, Zhou F, Zhang G, Rostami A (2011) Kit (W-sh) mice develop earlier and more severe experimental autoimmune encephalomyelitis due to absence of immune suppression. J Immunol 187:274–282
Lindsberg PJ, Strbian D, Karjalainen-Lindsberg ML (2010) Mast cells as early responders in the regulation of acute blood–brain barrier changes after cerebral ischemia and hemorrhage. J Cereb Blood Flow Metab 30:689–702
Lindstedt KA, Wang Y, Shiota N, Saarinen J, Hyytiäinen M, Kokkonen JO, Keski-Oja J, Kovanen PT (2001) Activation of paracrine TGF-beta1 signaling upon stimulation and degranulation of rat serosal mast cells: a novel function for chymase. FASEB J 15:1377–1388
Liu J, Divoux A, Sun J, Zhang J, Clément K, Glickman JN, Sukhova GK, Wolters PJ, Du J, Gorgun CZ, Doria A, Libby P, Blumberg RS, Kahn BB, Hotamisligil GS, Shi GP (2009) Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 15:940–945
Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, Langer-Gould A, Strober S, Cannella B, Allard J, Klonowski P, Austin A, Lad N, Kaminski N, Galli SJ, Oksenberg JR, Raine CS, Heller R, Steinman L (2002) Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 8:500–508
Lowman MA, Rees PH, Benyon RC, Church MK (1988) Human mast cell heterogeneity: histamine release from mast cells dispersed from skin, lung, adenoids, tonsils, and colon in response to IgE-dependent and nonimmunologic stimuli. J Allergy Clin Immunol 81:590–597
Lyon MF, Glenister PH (1982) A new allele sash (Wsh) at the W-locus and a spontaneous recessive lethal in mice. Genet Res 39:315–322
MacLean MR, Dempsie Y (2009) Serotonin and pulmonary hypertension–from bench to bedside? Curr Opin Pharmacol 9:281–286
Magnusson SE, Pejler G, Kleinau S, Abrink M (2009) Mast cell chymase contributes to the antibody response and the severity of autoimmune arthritis. FASEB J 23:875–882
Majeed SK (1994) Mast cell distribution in mice. Arzneimittelforschung 44:1170–1173
Manchanda RK, Jaggi AS, Singh N (2011) Ameliorative potential of sodium cromoglycate and diethyldithiocarbamic acid in restraint stress-induced behavioral alterations in rats. Pharmacol Rep 63:54–63
Maruotti N, Crivellato E, Cantatore FP, Vacca A, Ribatti D (2007) Mast cells in rheumatoid arthritis. Clin Rheumatol 26:1–4
Maslinska D, Laure-Kamionowska M, Maslinski KT, Gujski M, Maslinski S (2007) Distribution of tryptase-containing mast cells and metallothionein reactive astrocytes in human brains with amyloid deposits. Inflamm Res 56(Suppl 1):S17–S18
Matsuda H, Kawakita K, Kiso Y, Nakano T, Kitamura Y (1989) Substance P induces granulocyte infiltration through degranulation of mast cells. J Immunol 142:927–931
Mattila OS, Strbian D, Saksi J, Pikkarainen TO, Rantanen V, Tatlisumak T, Lindsberg PJ (2011) Cerebral mast cells mediate blood–brain barrier disruption in acute experimental ischemic stroke through perivascular gelatinase activation. Stroke 42:3600–3605
Maxová H, Vasilková M, Novotná J, Vajnerová O, Bansová A, Vízek M, Herget J (2010) Prevention of mast cell degranulation by disodium cromoglycate delayed the regression of hypoxic pulmonary hypertension in rats. Respiration 80:335–339
McNeil HP, Shin K, Campbell IK, Wicks IP, Adachi R, Lee DM, Stevens RL (2008) The mouse mast cell-restricted tetramer-forming tryptases mouse mast cell protease 6 and mouse mast cell protease 7 are critical mediators in inflammatory arthritis. Arthritis Rheum 58:2338–2346
Menzies FM, Shepherd MC, Nibbs RJ, Nelson SM (2011) The role of mast cells and their mediators in reproduction, pregnancy and labour. Hum Reprod Update 17:383–396
Miettinen M, Lasota J (2005) KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol 13:205–220
Mitani Y, Ueda M, Maruyama K, Shimpo H, Kojima A, Matsumura M, Aoki K, Sakurai M (1999) Mast cell chymase in pulmonary hypertension. Thorax 54:88–90
Miyata M, Sakuma F, Ito M, Ohira H, Sato Y, Kasukawa R (2000) Athymic nude rats develop severe pulmonary hypertension following monocrotaline administration. Int Arch Allergy Immunol 121:246–252
Montani D, Perros F, Gambaryan N, Girerd B, Dorfmuller P, Price LC, Huertas A, Hammad H, Lambrecht B, Simonneau G, Launay JM, Cohen-Kaminsky S, Humbert M (2011) C-kit-positive cells accumulate in remodeled vessels of idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 184:116–123
Morrell NW, Morris KG, Stenmark KR (1995) Role of angiotensin-converting enzyme and angiotensin II in development of hypoxic pulmonary hypertension. Am J Physiol 269:H1186–H1194
Nautiyal KM, Ribeiro AC, Pfaff DW, Silver R (2008) Brain mast cells link the immune system to anxiety-like behavior. Proc Natl Acad Sci USA 105:18053–18057
Nelson RB, Siman R, Iqbal MA, Potter H (1993) Identification of a chymotrypsin-like mast cell protease in rat brain capable of generating the N-terminus of the Alzheimer amyloid beta-protein. J Neurochem 61:567–577
Niederhoffer N, Levy R, Sick E, Andre P, Coupin G, Lombard Y, Gies JP (2009) Amyloid beta peptides trigger CD47-dependent mast cell secretory and phagocytic responses. Int J Immunopathol Pharmacol 22:473–483
Oberpenning F, van Ophoven A, Hertle L (2002) Interstitial cystitis: an update. Curr Opin Urol 12:321–332
Okoń K, Stachura J (2007) Increased mast cell density in renal interstitium is correlated with relative interstitial volume, serum creatinine and urea especially in diabetic nephropathy but also in primary glomerulonephritis. Pol J Pathol 58:193–197
Oksjoki R, Laine P, Helske S, Vehmaan-Kreula P, Mäyränpää MI, Gasque P, Kovanen PT, Pentikäinen MO (2007) Receptors for the anaphylatoxins C3a and C5a are expressed in human atherosclerotic coronary plaques. Atherosclerosis 195:90–99
Oliva A, Multigner L (2006) Ketotifen improves sperm motility and sperm morphology in male patients with leukocytospermia and unexplained infertility. Fertil Steril 85:240–243
Ortiz-Lucas M, Saz-Peiró P, Sebastián-Domingo JJ (2010) Irritable bowel syndrome immune hypothesis. Part one: the role of lymphocytes and mast cells. Rev Esp Enferm Dig 102:637–647
Paananen K, Kovanen PT (1994) Proteolysis and fusion of low density lipoprotein particles independently strengthen their binding to exocytosed mast cell granules. J Biol Chem 269:2023–2031
Paniagua RT, Sharpe O, Ho PP, Chan SM, Chang A, Higgins JP, Tomooka BH, Thomas FM, Song JJ, Goodman SB, Lee DM, Genovese MC, Utz PJ, Steinman L, Robinson WH (2006) Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis. J Clin Invest 116:2633–2642
Parada CA, Tambeli CH, Cunha FQ, Ferreira SH (2001) The major role of peripheral release of histamine and 5-hydroxytryptamine in formalin induced nociception. Neuroscience 102:937–944
Parikh V, Singh M (1998) Cardiac mast cell stabilization and cardioprotective effect of ischaemic preconditioning in isolated rat heart. J Cardiovas Pharmacol 31:779–785
Park CS, Bochner BS (2011) Potential targeting of siglecs, mast cell inhibitory receptors, in interstitial cystitis. Int Neurourol J 15:61–63
Parnham MJ (1996) Sodium cromoglycate and nedocromil sodium in the therapy of asthma, a critical comparison. Pulm Pharmacol 9:95–105
Pedinoff AJ (1996) Approaches to the treatment of seasonal allergic rhinitis. South Med J 89:1130–1139
Pejler G, Abrink M, Ringvall M, Wernersson S (2007) Mast cell proteases. Adv Immunol 95:167–2550
Piche T, Saint-Paul MC, Dainese R, Marine-Barjoan E, Iannelli A, Montoya ML, Peyron JF, Czerucka D, Cherikh F, Filippi J, Tran A, Hébuterne X (2008) Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut 57:468–473
Piconese S, Costanza M, Musio S, Tripodo C, Poliani PL, Gri G, Burocchi A, Pittoni P, Gorzanelli A, Colombo MP, Pedotti R (2011) Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit W-sh/W-sh mice. Lab Invest 91:627–641
Piette F, Belmin J, Vincent H, Schmidt N, Pariel S, Verny M, Marquis C, Mely J, Hugonot-Diener L, Kinet JP, Dubreuil P, Moussy A, Hermine O (2011) Masitinib as an adjunct therapy for mild-to-moderate Alzheimer’s disease: a randomised, placebo-controlled phase 2 trial. Alzheimers Res Ther 3:16
Pimentel TA, Sampaio AL, D’Acquisto F, Perretti M, Oliani SM (2011) An essential role for mast cells as modulators of neutrophils influx in collagen-induced arthritis in the mouse. Lab Invest 91:33–42
Pittoni P, Tripodo C, Piconese S, Mauri G, Parenza M, Rigoni A, Sangaletti S, Colombo MP (2011) Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers. Cancer Res 71:5987–5997
Plaut M, Pierce HJ, Watson CJ (1989) Mast cells lines produce lymphokines in response to cross linkage of FcERI or to calcium ionophores. Nature 339:64–75
Rehni AK, Bhateja P, Singh N, Jaggi AS (2008) Implication of mast cell degranulation in ischemic preconditioning-induced prevention of cerebral injury. Fundam Clin Pharmacol 22:179–188
Reichel CA, Lerchenberger M, Uhl B, Rehberg M, Berberich N, Zahler S, Wymann MP, Krombach F (2011) Plasmin inhibitors prevent leukocyte accumulation and remodeling events in the postischemic microvasculature. PLoS One 6:e17229
Ren G, Dewald O, Frangogiannis NG (2003) Inflammatory mechanisms in myocardial infarction. Curr Drug Targets Inflamm Allergy 2:242–256
Ribatti D, Crivellato E (2009) The controversial role of mast cells in tumor growth. Int Rev Cell Mol Biol 275:89–131
Ribatti D, Ennas MG, Vacca A, Ferreli F, Nico B, Orru S, Sirigu P (2003) Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma. Eur J Clin Invest 33:420–425
Richter B, Roslind A, Hesse U, Nordling J, Johansen JS, Horn T, Hansen AB (2010) YKL-40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis. Histopathology 57:371–383
Rozniecki JJ, Hauser SL, Stein M, Lincoln R, Theoharides TC (1995) Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients. Ann Neurol 37:63–66
Rudick CN, Bryce PJ, Guichelaar LA, Berry RE, Klumpp DJ (2008) Mast cell-derived histamine mediates cystitis pain. PLoS One 3:e2096
Saban R, Gerard NP, Saban MR, Nguyen NB, DeBoer DJ, Wershil BK (2002) Mast cells mediate substance P-induced bladder inflammation through an NK(1) receptor-independent mechanism. Am J Physiol Renal Physiol 283:F616–F629
Samoszuk M, Kanakubo E, Chan JK (2005) Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts. BMC Cancer 5:121
Sand E, Themner-Persson A, Ekblad E (2008) Infiltration of mast cells in rat colon is a consequence of ischemia/reperfusion. Dig Dis Sci 53:3158–3169
Sandkühler J (2009) Models and mechanisms of hyperalgesia and allodynia. Physiol Rev 89:707–758
Sant GR, Kempuraj D, Marchand JE, Theoharides TC (2007) The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis. Urology 69:34–40
Santen S, Wang Y, Menger MD, Jeppsson B, Thorlacius H (2008) Mast-cell-dependent secretion of CXC chemokines regulates ischemia-reperfusion-induced leukocyte recruitment in the colon. Int J Colorectal Dis 23:527–534
Sawamukai N, Yukawa S, Saito K, Nakayamada S, Kambayashi T, Tanaka Y (2010) Mast cell-derived tryptase inhibits apoptosis of human rheumatoid synovial fibroblasts via rho-mediated signaling. Arthritis Rheum 62:952–959
Sayed BA, Christy AL, Walker ME, Brown MA (2010) Meningeal mast cells affect early T cell central nervous system infiltration and blood–brain barrier integrity through TNF: a role for neutrophil recruitment? J Immunol 184:6891–6900
Sayed BA, Walker ME, Brown MA (2011) Cutting edge: mast cells regulate disease severity in a relapsing-remitting model of multiple sclerosis. J Immunol 186:3294–3298
Schwartz LB, Austen KF (1980) Enzymes of the mast cell granules. J Invest Dermatol 74:349–353
Secor VH, Secor WE, Gutekunst CA, Brown MA (2000) Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis. J Exp Med 191:813–822
Sezer C, Koksal IT, Usta MF, Gulkesen KH, Erdogru T, Ciftcioglu A, Baykara M (2005) Relationship between mast cell and iNOS expression in testicular tissue associated with infertility. Arch Androl 51:149–158
Sharma K, Ziyadeh FN (1993) The transforming growth factor-beta system and the kidney. Semin Nephrol 13:116–128
Shie JH, Kuo HC (2011) Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome. BJU Int 108:E136–E141
Shin K, Nigrovic PA, Crish J, Boilard E, McNeil HP, Larabee KS, Adachi R, Gurish MF, Gobezie R, Stevens RL, Lee DM (2009) Mast cells contribute to autoimmune inflammatory arthritis via their tryptase/heparin complexes. J Immunol 182:647–656
Shiota N, Kovanen PT, Eklund KK, Shibata N, Shimoura K, Niibayashi T, Shimbori C, Okunishi H (2010) The anti-allergic compound tranilast attenuates inflammation and inhibits bone destruction in collagen-induced arthritis in mice. Br J Pharmacol 159:626–635
Singh M, Saini HK (2003) Resident cardiac mast cells and ischemia-reperfusion injury. J Cardiovasc Pharmacol Ther 8:135–148
Sinnamon MJ, Carter KJ, Sims LP, Lafleur B, Fingleton B, Matrisian LM (2008) A protective role of mast cells in intestinal tumorigenesis. Carcinogenesis 29:880–886
Soucek L, Lawlor ER, Soto D, Shchors K, Swigart LB, Evan GI (2007) Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat Med 13:1211–1218
Sperr WR, Bankl HC, Mundigler G, Klappacher G, Grossschmidt K, Agis H, Simon P, Laufer P, Imhof M, Radaszkiewicz T, Glogar D, Lechner K, Valent P (1994) The human cardiac mast cell: localization, isolation, phenotype, and functional characterization. Blood 84:3876–3884
Stead RH, Dixon MF, Bramwell NH, Riddell RH, Bienenstock J (1989) Mast cells are closely apposed to nerves in the human gastrointestinalmucosa. Gastroenterology 97:575–585
Stoyanov E, Uddin M, Mankuta D, Dubinett SM, Levi-Schaffer F (2012) Mast cells and histamine enhance the proliferation of non-small cell lung cancer cells. Lung Cancer 75:38–44
Strbian D, Kovanen PT, Karjalainen-Lindsberg ML, Tatlisumak T, Lindsberg PJ (2009) An emerging role of mast cells in cerebral ischemia and hemorrhage. Ann Med 41:438–450
Sun J, Sukhova GK, Wolters PJ, Yang M, Kitamoto S, Libby P, MacFarlane LA, Mallen-St Clair J, Shi GP (2007) Mast cells promote atherosclerosis by releasing proinflammatory cytokines. Nat Med 13:719–724
Suurmond J, Dorjee AL, Boon MR, Knol EF, Huizinga TW, Toes RE, Schuerwegh AJ (2011) Mast cells are the main interleukin-17-positive cells in anti-citrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium. Arthritis Res Ther 13:R150
Suzuki A, Suzuki R, Furuno T, Teshima R, Nakanishi M (2004) N-cadherin plays a role in the synapse-like structures between mast cells and neurites. Biol Pharm Bull 27:1891–1894
Taiwo OB, Kovács KJ, Sun Y, Larson AA (2005) Unilateral spinal nerve ligation leads to an asymmetrical distribution of mast cells in the thalamus of female but not male mice. Pain 114:131–140
Tajima Y, Hamada K, Houzenn H, Tsukishima E, Owada Y, Moriwaka F, Musashi M, Miyazaki T, Hamada T, Tashiro K (1994) Sequential magnetic resonance features of encephalopathy induced by systemic mastocytosis. Intern Med 33:23–26
Tang YL, Yang YZ, Wang S, Huang T, Tang CK, Xu ZX, Sun YH (2009) Mast cell degranulator compound 48–80 promotes atherosclerotic plaque in apolipoprotein E knockout mice with perivascular common carotid collar placement. Chin Med J (Engl) 122:319–325
Tchougounova E, Lundequist A, Fajardo I, Winberg JO, Abrink M, Pejler G (2005) A key role for mast cell chymase in the activation of pro-matrix metalloprotease-9 and pro-matrix metalloprotease-2. J Biol Chem 280:9291–9296
Theoharides TC (2009) Luteolin as a therapeutic option for multiple sclerosis. J Neuroinflammation 6:29
Theoharides TC, Kempuraj D, Sant GR (2001) Mast cell involvement in interstitial cystitis: a review of human and experimental evidence. Urology 57:47–55
Theoharides TC, Donelan J, Kandere-Grzybowska K, Konstantinidou A (2005) The role of mast cells in migraine pathophysiology. Brain Res Brain Res Rev 49:65–76
Theoharides TC, Kempuraj D, Kourelis T, Manola A (2008) Human mast cells stimulate activated T cells: implications for multiple sclerosis. Ann N Y Acad Sci 1144:74–82
Theoharides TC, Sismanopoulos N, Delivanis DA, Zhang B, Hatziagelaki EE, Kalogeromitros D (2011) Mast cells squeeze the heart and stretch the gird: their role in atherosclerosis and obesity. Trends Pharmacol Sci 32:534–542
Traver E, Torres R, de Mora F, Vergara P (2010) Mucosal mast cells mediate motor response induced by chronic oral exposure to ovalbumin in the rat gastrointestinal tract. Neurogastroenterol Motil 22:e34–e43
van Diest SA, Stanisor OI, Boeckxstaens GE, de Jonge WJ, van den Wijngaard RM (2012) Relevance of mast cell–nerve interactions in intestinal nociception. Biochim Biophys Acta 1822:74–84
Vicario M, Guilarte M, Alonso C, Yang P, Martínez C, Ramos L, Lobo B, González A, Guilà M, Pigrau M, Saperas E, Azpiroz F, Santos J (2010) Chronological assessment of mast cell-mediated gut dysfunction and mucosal inflammation in a rat model of chronic psychosocial stress. Brain Behav Immun 24:1166–1175
Walker MM, Warwick A, Ung C, Talley NJ (2011) The role of eosinophils and mast cells in intestinal functional disease. Curr Gastroenterol Rep 13:323–330
Walker ME, Hatfield JK, Brown MA (2012) New insights into the role of mast cells in autoimmunity: evidence for a common mechanism of action? Biochim Biophys Acta 1822:57–65
Wang J, Shi GP (2011) Mast cell stabilization: novel medication for obesity and diabetes. Diabetes Metab Res Rev 27:919–924
Wei JJ, Song CW, Sun LC, Yuan Y, Li D, Yan B, Liao SJ, Zhu JH, Wang Q, Zhang GM, Feng ZH (2012) SCF and TLR4 ligand cooperate to augment the tumor-promoting potential of mast cells. Cancer Immunol Immunother 61:303–312
Wilhelm M, Silver R, Silverman AJ (2005) Central nervous system neurons acquire mast cell products via transgranulation. Eur J Neurosci 22:2238–2248
Xanthos DN, Gaderer S, Drdla R, Nuro E, Abramova A, Ellmeier W, Sandkühler J (2011) Central nervous system mast cells in peripheral inflammatory nociception. Mol Pain 7:42
Yong T, Bebo BF Jr, Sapatino BV, Welsh CJ, Orr EL, Linthicum DS (1994) Histamine-induced microvascular leakage in pial venules: differences between the SJL/J and BALB/c inbred strains of mice. J Neurotrauma 11:161–171
Yu S, Kollarik M, Ouyang A, Myers AC, Undem BJ (2007) Mast cell mediated long-lasting increases in excitability of vagal C-fibers in guinea pig esophagus. Am J Physiol Gastrointest Liver Physiol 293:G850–G856
Yu S, Gao G, Peterson BZ, Ouyang A (2009) TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus. Am J Physiol Gastrointest Liver Physiol 297:G34–G42
Zhang J, Shi GP (2012) Mast cells and metabolic syndrome. Biochim Biophys Acta 1822:14–20
Zheng JM, Yao GH, Cheng Z, Wang R, Liu ZH (2012) Pathogenic role of mast cells in the development of diabetic nephropathy: a study of patients at different stages of the disease. Diabetologia 55:801–811
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The authors are grateful to Punjabi University, Patiala, India for supporting this study and providing technical facilities for the work.
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Anand, P., Singh, B., Jaggi, A.S. et al. Mast cells: an expanding pathophysiological role from allergy to other disorders. Naunyn-Schmiedeberg's Arch Pharmacol 385, 657–670 (2012). https://doi.org/10.1007/s00210-012-0757-8
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DOI: https://doi.org/10.1007/s00210-012-0757-8