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Fibrocytes and Pulmonary Vascular Remodeling: The Good, the Bad, and the Progenitors

  • Chapter
Lung Stem Cells in the Epithelium and Vasculature

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Pulmonary vascular remodeling (PVR) is a definitive characteristic of diseases associated with physiological and pathobiological changes that present themselves in the lung vasculature(s). The primary diseases associated with PVR are pulmonary edema and pulmonary hypertension (PH), which is a prevalent disease of many etiologies. The lymphatic system is important in maintaining tissue homeostasis and its vasculature provides a means of interface between the immune cells and the external lung environment. The discussion of PVR leads into proximal and distal vessel remodeling in a miscellany of disease contexts. Along with an in-depth look into the topics outlined above, the chapter further provides insight into fibrocytes: their history, phenotypic description, their functional role in inflammation, and differentiation. We conclude the chapter by posing an important question: “Fibrocytes, a bone-marrow derived cell population, are they stem cells, or progenitor cells?” and provide evidence for and against whether fibrocytes modulate and contribute to PVR.

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Abbreviations

BALT:

Bronchus-associated lymphoid tissue

CD11b:

Cluster of differentiation factor 11b (aka integrin alpha M (ITGAM))

CD45:

Cluster of differentiation factor 45 (aka protein tyrosine phosphatase, receptor type, C (PTPRC))

COPD:

Chronic obstructive pulmonary disease

ECM:

Extracellular matrix

EGPA:

Eosinophilic granulomatosis with polyangiitis

FEV1:

Forced expiratory volume exhaled in 1 s

HLA-DR:

Human leukocyte antigen-DR (MHC class II cell surface receptor)

ICAM-1:

Intracellular adhesion molecule 1 (aka CD54)

IL:

Interleukin

IPAH:

Idiopathic pulmonary arterial hypertension

IPF:

Idiopathic pulmonary fibrosis

MHC:

Major histocompatibility complex

MMP:

Matrix metalloprotease

PA:

Pulmonary artery

PAH:

Pulmonary arterial hypertension

PBMC:

Peripheral blood mononuclear cell

PG:

Proteoglycan

PH:

Pulmonary hypertension

PVR:

Pulmonary vascular remodeling

RFP:

Red fluorescent protein

SAP:

Serum amyloid P

SMA:

Smooth muscle actin

References

  • Abe R, Donnelly SC, Peng T, Bucala R, Metz CN (2001) Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol 166(12):7556–7562

    CAS  PubMed  Google Scholar 

  • Adams J, Harris A, Strasser A, Ogilvy S, Cory S (1999) Transgenic models of lymphoid neoplasia and development of a pan-hematopoietic vector. Oncogene 18(38):5268–5277

    CAS  PubMed  Google Scholar 

  • Aggarwal NR, King LS, D’Alessio FR (2014) Diverse macrophage populations mediate acute lung inflammation and resolution. Am J Physiol Lung Cell Mol Physiol 306(8):L709–L725. doi:10.1152/ajplung.00341.2013

    PubMed Central  CAS  PubMed  Google Scholar 

  • Aiba S, Tagami H (1997) Inverse correlation between CD34 expression and proline-4-hydroxylase immunoreactivity on spindle cells noted in hypertrophic scars and keloids. J Cutan Pathol 24(2):65–69

    CAS  PubMed  Google Scholar 

  • Alagappan VK, de Boer WI, Misra VK, Mooi WJ, Sharma HS (2013) Angiogenesis and vascular remodeling in chronic airway diseases. Cell Biochem Biophys 67(2):219–234. doi:10.1007/s12013-013-9713-6

    CAS  PubMed  Google Scholar 

  • Al-Jamal R, Ludwig MS (2001) Changes in proteoglycans and lung tissue mechanics during excessive mechanical ventilation in rats. Am J Physiol Lung Cell Mol Physiol 281(5):L1078–L1087

    CAS  PubMed  Google Scholar 

  • Archer SL, Weir EK, Wilkins MR (2010) Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation 121(18):2045–2066. doi:10.1161/CIRCULATIONAHA.108.847707

    PubMed Central  PubMed  Google Scholar 

  • Avdalovic M (2015) Pulmonary vasculature and critical asthma syndromes: a comprehensive review. Clin Rev Allergy Immunol 48(1):97–103. doi:10.1007/s12016-014-8420-4

    CAS  PubMed  Google Scholar 

  • Avdalovic MV, Putney LF, Schelegle ES, Miller L, Usachenko JL, Tyler NK, Plopper CG, Gershwin LJ, Hyde DM (2006) Vascular remodeling is airway generation-specific in a primate model of chronic asthma. Am J Respir Crit Care Med 174(10):1069–1076. doi:10.1164/rccm.200506-848OC

    PubMed Central  CAS  PubMed  Google Scholar 

  • Barisic‐Dujmovic T, Boban I, Clark SH (2010) Fibroblasts/myofibroblasts that participate in cutaneous wound healing are not derived from circulating progenitor cells. J Cell Physiol 222(3):703–712

    PubMed  Google Scholar 

  • Behrendt N, Jensen ON, Engelholm LH, Mørtz E, Mann M, Danø K (2000) A urokinase receptor-associated protein with specific collagen binding properties. J Biol Chem 275(3):1993–2002

    CAS  PubMed  Google Scholar 

  • Bellini A, Mattoli S (2007) The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses. Lab Invest 87(9):858–870

    CAS  PubMed  Google Scholar 

  • Bellini A, Marini MA, Bianchetti L, Barczyk M, Schmidt M, Mattoli S (2012) Interleukin (IL)-4, IL-13, and IL-17A differentially affect the profibrotic and proinflammatory functions of fibrocytes from asthmatic patients. Mucosal Immunol 5(2):140–149. doi:10.1038/mi.2011.60

    CAS  PubMed  Google Scholar 

  • Bianchetti L, Barczyk M, Cardoso J, Schmidt M, Bellini A, Mattoli S (2012) Extracellular matrix remodelling properties of human fibrocytes. J Cell Mol Med 16(3):483–495

    PubMed Central  CAS  PubMed  Google Scholar 

  • Brotons ML, Bolca C, Frechette E, Deslauriers J (2012) Anatomy and physiology of the thoracic lymphatic system. Thorac Surg Clin 22(2):139–153. doi:10.1016/j.thorsurg.2011.12.002

    PubMed  Google Scholar 

  • Brown J, Greaves M, Molgaard H (1991) The gene encoding the stem cell antigen, CD34, is conserved in mouse and expressed in haemopoietic progenitor cell lines, brain, and embryonic fibroblasts. Int Immunol 3(2):175–184

    CAS  PubMed  Google Scholar 

  • Bucala R, Spiegel L, Chesney J, Hogan M, Cerami A (1994) Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1(1):71

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bustelo X, Rubin S, Suen K, Carrasco D, Barbacid M (1993) Developmental expression of the vav protooncogene. Cell Growth Differ 4(4):297–308

    CAS  PubMed  Google Scholar 

  • Carmier D, Marchand-Adam S, Diot P, Diot E (2010) Respiratory involvement in systemic lupus erythematosus. Rev Mal Respir 27(8):e66–e78. doi:10.1016/j.rmr.2010.01.003

    CAS  PubMed  Google Scholar 

  • Chesney J, Bacher M, Bender A, Bucala R (1997) The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T cells in situ. Proc Natl Acad Sci U S A 94(12):6307–6312

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chesney J, Metz C, Stavitsky AB, Bacher M, Bucala R (1998) Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes. J Immunol 160(1):419–425

    CAS  PubMed  Google Scholar 

  • Choi YH, Burdick MD, Strieter RM (2010) Human circulating fibrocytes have the capacity to differentiate osteoblasts and chondrocytes. Int J Biochem Cell Biol 42(5):662–671

    PubMed Central  CAS  PubMed  Google Scholar 

  • Churg J, Strauss L (1951) Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Pathol 27(2):277–301

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cohen-Kaminsky S, Hautefort A, Price L, Humbert M, Perros F (2014) Inflammation in pulmonary hypertension: what we know and what we could logically and safely target first. Drug Discov Today 19(8):1251–1256. doi:10.1016/j.drudis.2014.04.007

    CAS  PubMed  Google Scholar 

  • Colvin KL, Cripe PJ, Ivy DD, Stenmark KR, Yeager ME (2013) Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies. Am J Respir Crit Care Med 188(9):1126–1136. doi:10.1164/rccm.201302-0403OC

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cordeiro JV, Jacinto A (2013) The role of transcription-independent damage signals in the initiation of epithelial wound healing. Nat Rev Mol Cell Biol 14(4):249–262

    CAS  Google Scholar 

  • Cosgrove GP, Brown KK, Schiemann WP, Serls AE, Parr JE, Geraci MW, Schwarz MI, Cool CD, Worthen GS (2004) Pigment epithelium-derived factor in idiopathic pulmonary fibrosis: a role in aberrant angiogenesis. Am J Respir Crit Care Med 170(3):242–251. doi:10.1164/rccm.200308-1151OC

    PubMed  Google Scholar 

  • Crawford JR, Pilling D, Gomer RH (2012) FcgammaRI mediates serum amyloid P inhibition of fibrocyte differentiation. J Leukoc Biol 92(4):699–711. doi:10.1189/jlb.0112033

    PubMed Central  CAS  PubMed  Google Scholar 

  • Curnow SJ, Fairclough M, Schmutz C, Kissane S, Denniston AK, Nash K, Buckley CD, Lord JM, Salmon M (2010) Distinct types of fibrocyte can differentiate from mononuclear cells in the presence and absence of serum. PLoS One 5(3):e9730

    PubMed Central  PubMed  Google Scholar 

  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317. doi:10.1080/14653240600855905

    CAS  PubMed  Google Scholar 

  • Ebina M, Shimizukawa M, Shibata N, Kimura Y, Suzuki T, Endo M, Sasano H, Kondo T, Nukiwa T (2004) Heterogeneous increase in CD34-positive alveolar capillaries in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 169(11):1203–1208. doi:10.1164/rccm.200308-1111OC

    PubMed  Google Scholar 

  • Engelholm LH, List K, Netzel-Arnett S, Cukierman E, Mitola DJ, Aaronson H, Kjøller L, Larsen JK, Yamada KM, Strickland DK (2003) uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion. J Cell Biol 160(7):1009–1015

    PubMed Central  CAS  PubMed  Google Scholar 

  • Evans MJ, Van Winkle LS, Fanucchi MV, Plopper CG (1999) The attenuated fibroblast sheath of the respiratory tract epithelial-mesenchymal trophic unit. Am J Respir Cell Mol Biol 21(6):655–657. doi:10.1165/ajrcmb.21.6.3807

    CAS  PubMed  Google Scholar 

  • Farkas L, Gauldie J, Voelkel NF, Kolb M (2011) Pulmonary hypertension and idiopathic pulmonary fibrosis: a tale of angiogenesis, apoptosis, and growth factors. Am J Respir Cell Mol Biol 45(1):1–15. doi:10.1165/rcmb.2010-0365TR

    CAS  PubMed  Google Scholar 

  • Fathke C, Wilson L, Hutter J, Kapoor V, Smith A, Hocking A, Isik F (2004) Contribution of bone marrow-derived cells to skin: collagen deposition and wound repair. Stem Cells 22(5):812–822

    PubMed Central  PubMed  Google Scholar 

  • Gan Y, Reilkoff R, Peng X, Russell T, Chen Q, Mathai SK, Homer R, Gulati M, Siner J, Elias J, Bucala R, Herzog E (2011) Role of semaphorin 7a signaling in transforming growth factor beta1-induced lung fibrosis and scleroderma-related interstitial lung disease. Arthritis Rheum 63(8):2484–2494. doi:10.1002/art.30386

    PubMed Central  CAS  PubMed  Google Scholar 

  • Garantziotis S, Zudaire E, Trempus CS, Hollingsworth JW, Jiang D, Lancaster LH, Richardson E, Zhuo L, Cuttitta F, Brown KK, Noble PW, Kimata K, Schwartz DA (2008) Serum inter-alpha-trypsin inhibitor and matrix hyaluronan promote angiogenesis in fibrotic lung injury. Am J Respir Crit Care Med 178(9):939–947. doi:10.1164/rccm.200803-386OC

    PubMed Central  CAS  PubMed  Google Scholar 

  • Geissmann F, Auffray C, Palframan R, Wirrig C, Ciocca A, Campisi L, Narni-Mancinelli E, Lauvau G (2008) Blood monocytes: distinct subsets, how they relate to dendritic cells, and their possible roles in the regulation of T-cell responses. Immunol Cell Biol 86(5):398–408

    CAS  PubMed  Google Scholar 

  • Grieb G, Steffens G, Pallua N, Bernhagen J, Bucala R (2011) Circulating fibrocytes—biology and mechanisms in wound healing and scar formation. Int Rev Cell Mol Biol 291:1–19. doi:10.1016/B978-0-12-386035-4.00001-X

    CAS  PubMed  Google Scholar 

  • Grunig G, Marsh LM, Esmaeil N, Jackson K, Gordon T, Reibman J, Kwapiszewska G, Park SH (2014) Perspective: ambient air pollution: inflammatory response and effects on the lung’s vasculature. Pulm Circ 4(1):25–35. doi:10.1086/674902

    PubMed Central  PubMed  Google Scholar 

  • Guignabert C, Dorfmuller P (2013) Pathology and pathobiology of pulmonary hypertension. Semin Respir Crit Care Med 34(5):551–559. doi:10.1055/s-0033-1356496

    PubMed  Google Scholar 

  • Hanumegowda C, Farkas L, Kolb M (2012) Angiogenesis in pulmonary fibrosis: too much or not enough? Chest 142(1):200–207. doi:10.1378/chest.11-1962

    CAS  PubMed  Google Scholar 

  • Hayashi H, Kawakita A, Okazaki S, Murai H, Yasutomi M, Ohshima Y (2014) IL-33 enhanced the proliferation and constitutive production of IL-13 and IL-5 by fibrocytes. Biomed Res Int 2014:738625. doi:10.1155/2014/738625

    PubMed Central  PubMed  Google Scholar 

  • Heath D, Edwards JE (1958) The pathology of hypertensive pulmonary vascular disease: a description of six grades of structural changes in the pulmonary arteries with special reference to congenital cardiac septal defects. Circulation 18(4 Part 1):533–547

    CAS  PubMed  Google Scholar 

  • Hirose J, Kawashima H, Yoshie O, Tashiro K, Miyasaka M (2001) Versican interacts with chemokines and modulates cellular responses. J Biol Chem 276(7):5228–5234

    CAS  PubMed  Google Scholar 

  • Hong KM, Burdick MD, Phillips RJ, Heber D, Strieter RM (2005) Characterization of human fibrocytes as circulating adipocyte progenitors and the formation of human adipose tissue in SCID mice. FASEB J 19(14):2029–2031

    CAS  PubMed  Google Scholar 

  • Hong KM, Belperio JA, Keane MP, Burdick MD, Strieter RM (2007) Differentiation of human circulating fibrocytes as mediated by transforming growth factor-β and peroxisome proliferator-activated receptor γ. J Biol Chem 282(31):22910–22920

    CAS  PubMed  Google Scholar 

  • Howell SJ, Doane KJ (1998) Type VI collagen increases cell survival and prevents anti-β1 integrin-mediated apoptosis. Exp Cell Res 241(1):230–241

    CAS  PubMed  Google Scholar 

  • Hutchinson WL, Hohenester E, Pepys MB (2000) Human serum amyloid P component is a single uncomplexed pentamer in whole serum. Mol Med 6(6):482–493

    PubMed Central  CAS  PubMed  Google Scholar 

  • Iozzo RV (1998) Matrix proteoglycans: from molecular design to cellular function. Annu Rev Biochem 67(1):609–652

    CAS  PubMed  Google Scholar 

  • Kendall RT, Feghali-Bostwick CA (2014) Fibroblasts in fibrosis: novel roles and mediators. Front Pharmacol 5:123. doi:10.3389/fphar.2014.00123

    PubMed Central  PubMed  Google Scholar 

  • Kisseleva T, von Kockritz-Blickwede M, Reichart D, McGillvray SM, Wingender G, Kronenberg M, Glass CK, Nizet V, Brenner DA (2011) Fibrocyte-like cells recruited to the spleen support innate and adaptive immune responses to acute injury or infection. J Mol Med 89(10):997–1013. doi:10.1007/s00109-011-0756-0

    PubMed Central  PubMed  Google Scholar 

  • Kolosionek E, Crosby A, Harhay MO, Morrell N, Butrous G (2010) Pulmonary vascular disease associated with schistosomiasis. Expert Rev Anti Infect Ther 8(12):1467–1473. doi:10.1586/eri.10.124

    CAS  PubMed  Google Scholar 

  • Kotsianidis I, Nakou E, Bouchliou I, Tzouvelekis A, Spanoudakis E, Steiropoulos P, Sotiriou I, Aidinis V, Margaritis D, Tsatalas C, Bouros D (2009) Global impairment of CD4+CD25+FOXP3+ regulatory T cells in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 179(12):1121–1130. doi:10.1164/rccm.200812-1936OC

    CAS  PubMed  Google Scholar 

  • Kotton DN, Ma BY, Cardoso WV, Sanderson EA, Summer RS, Williams MC, Fine A (2001) Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development 128(24):5181–5188

    CAS  PubMed  Google Scholar 

  • Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT (2010) Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science 330(6005):827–830. doi:10.1126/science.1195300

    CAS  PubMed  Google Scholar 

  • Kranenburg AR, De Boer WI, Van Krieken JH, Mooi WJ, Walters JE, Saxena PR, Sterk PJ, Sharma HS (2002) Enhanced expression of fibroblast growth factors and receptor FGFR-1 during vascular remodeling in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 27(5):517–525. doi:10.1165/rcmb.4474

    CAS  PubMed  Google Scholar 

  • Kranenburg AR, Willems-Widyastuti A, Mooi WJ, Saxena PR, Sterk PJ, de Boer WI, Sharma HS (2005) Chronic obstructive pulmonary disease is associated with enhanced bronchial expression of FGF-1, FGF-2, and FGFR-1. J Pathol 206(1):28–38. doi:10.1002/path.1748

    CAS  PubMed  Google Scholar 

  • Kranenburg AR, Willems-Widyastuti A, Moori WJ, Sterk PJ, Alagappan VK, de Boer WI, Sharma HS (2006) Enhanced bronchial expression of extracellular matrix proteins in chronic obstructive pulmonary disease. Am J Clin Pathol 126(5):725–735

    CAS  PubMed  Google Scholar 

  • Lee AH, Dhaliwal R, Kantores C, Ivanovska J, Gosal K, McNamara PJ, Letarte M, Jankov RP (2014) Rho-kinase inhibitor prevents bleomycin-induced injury in neonatal rats independent of effects on lung inflammation. Am J Respir Cell Mol Biol 50(1):61–73. doi:10.1165/rcmb.2013-0131OC

    PubMed  Google Scholar 

  • Li X, Wilson JW (1997) Increased vascularity of the bronchial mucosa in mild asthma. Am J Respir Crit Care Med 156(1):229–233. doi:10.1164/ajrccm.156.1.9607066

    CAS  PubMed  Google Scholar 

  • Li J, Tan H, Wang X, Li Y, Samuelson L, Li X, Cui C, Gerber DA (2014) Circulating fibrocytes stabilize blood vessels during angiogenesis in a paracrine manner. Am J Pathol 184(2):556–571. doi:10.1016/j.ajpath.2013.10.021

    CAS  PubMed  Google Scholar 

  • Madsen DH, Engelholm LH, Ingvarsen S, Hillig T, Wagenaar-Miller RA, Kjøller L, Gårdsvoll H, Høyer-Hansen G, Holmbeck K, Bugge TH (2007) Extracellular collagenases and the endocytic receptor, urokinase plasminogen activator receptor-associated protein/Endo180, cooperate in fibroblast-mediated collagen degradation. J Biol Chem 282(37):27037–27045

    CAS  PubMed  Google Scholar 

  • Maharjan AS, Pilling D, Gomer RH (2010) Toll-like receptor 2 agonists inhibit human fibrocyte differentiation. Fibrogenesis Tissue Repair 3:23. doi:10.1186/1755-1536-3-23

    PubMed Central  CAS  PubMed  Google Scholar 

  • Maharjan AS, Pilling D, Gomer RH (2011) High and low molecular weight hyaluronic acid differentially regulate human fibrocyte differentiation. PLoS One 6(10):e26078. doi:10.1371/journal.pone.0026078

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mattoli S, Bellini A, Schmidt M (2009) The role of a human hematopoietic mesenchymal progenitor in wound healing and fibrotic diseases and implications for therapy. Curr Stem Cell Res Ther 4(4):266–280

    CAS  PubMed  Google Scholar 

  • Miserocchi G (2009) Mechanisms controlling the volume of pleural fluid and extravascular lung water. Eur Respir Rev 18(114):244–252. doi:10.1183/09059180.00002709

    CAS  PubMed  Google Scholar 

  • Mitzner W, Wagner EM (2004) Vascular remodeling in the circulations of the lung. J Appl Physiol 97(5):1999–2004. doi:10.1152/japplphysiol.00473.2004

    PubMed  Google Scholar 

  • Molawi K, Sieweke MH (2013) Transcriptional control of macrophage identity, self-renewal, and function. Adv Immunol 120:269–300. doi:10.1016/B978-0-12-417028-5.00010-7

    CAS  PubMed  Google Scholar 

  • Moores SL, Selfors LM, Fredericks J, Breit T, Fujikawa K, Alt FW, Brugge JS, Swat W (2000) Vav family proteins couple to diverse cell surface receptors. Mol Cell Biol 20(17):6364–6373

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mori L, Bellini A, Stacey MA, Schmidt M, Mattoli S (2005) Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow. Exp Cell Res 304(1):81–90

    CAS  PubMed  Google Scholar 

  • Mousavi S, Sato M, Sporstol M, Smedsrod B, Berg T, Kojima N, Senoo H (2005) Uptake of denatured collagen into hepatic stellate cells: evidence for the involvement of urokinase plasminogen activator receptor-associated protein/Endo180. Biochem J 387:39–46

    PubMed Central  CAS  PubMed  Google Scholar 

  • Muller-Ladner U, Distler O, Ibba-Manneschi L, Neumann E, Gay S (2009) Mechanisms of vascular damage in systemic sclerosis. Autoimmunity 42(7):587–595

    PubMed  Google Scholar 

  • Murray LA, Rosada R, Moreira AP, Joshi A, Kramer MS, Hesson DP, Argentieri RL, Mathai S, Gulati M, Herzog EL, Hogaboam CM (2010) Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages. PLoS One 5(3):e9683. doi:10.1371/journal.pone.0009683

    PubMed Central  PubMed  Google Scholar 

  • Murray LA, Chen Q, Kramer MS, Hesson DP, Argentieri RL, Peng X, Gulati M, Homer RJ, Russell T, van Rooijen N, Elias JA, Hogaboam CM, Herzog EL (2011) TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. Int J Biochem Cell Biol 43(1):154–162. doi:10.1016/j.biocel.2010.10.013

    CAS  PubMed  Google Scholar 

  • Myllyharju J, Kivirikko KI (2001) Collagens and collagen-related diseases. Ann Med 33(1):7–21

    CAS  PubMed  Google Scholar 

  • Myllyharju J, Kivirikko KI (2004) Collagens, modifying enzymes and their mutations in humans, flies and worms. Trends Genet 20(1):33–43

    CAS  PubMed  Google Scholar 

  • Nikam VS, Schermuly RT, Dumitrascu R, Weissmann N, Kwapiszewska G, Morrell N, Klepetko W, Fink L, Seeger W, Voswinckel R (2010) Treprostinil inhibits the recruitment of bone marrow-derived circulating fibrocytes in chronic hypoxic pulmonary hypertension. Eur Respir J 36(6):1302–1314. doi:10.1183/09031936.00028009

    CAS  PubMed  Google Scholar 

  • Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG (2003) Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A 100(14):8407–8411. doi:10.1073/pnas.1432929100

    PubMed Central  CAS  PubMed  Google Scholar 

  • Peao MN, Aguas AP, de Sa CM, Grande NR (1994) Neoformation of blood vessels in association with rat lung fibrosis induced by bleomycin. Anat Rec 238(1):57–67. doi:10.1002/ar.1092380108

    CAS  PubMed  Google Scholar 

  • Peng X, Moore MW, Peng H, Sun H, Gan Y, Homer RJ, Herzog EL (2014) CD4+CD25+FoxP3+ Regulatory Tregs inhibit fibrocyte recruitment and fibrosis via suppression of FGF-9 production in the TGF-beta1 exposed murine lung. Front Pharmacol 5:80. doi:10.3389/fphar.2014.00080

    PubMed Central  PubMed  Google Scholar 

  • Perros F, Dorfmuller P, Montani D, Hammad H, Waelput W, Girerd B, Raymond N, Mercier O, Mussot S, Cohen-Kaminsky S, Humbert M, Lambrecht BN (2012) Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 185(3):311–321. doi:10.1164/rccm.201105-0927OC

    PubMed  Google Scholar 

  • Phillips RJ, Burdick MD, Hong K, Lutz MA, Murray LA, Xue YY, Belperio JA, Keane MP, Strieter RM (2004) Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest 114(3):438–446

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pilling D, Gomer RH (2014) Persistent lung inflammation and fibrosis in serum amyloid P component (APCs−/−) knockout mice. PLoS One 9(4):e93730. doi:10.1371/journal.pone.0093730

    PubMed Central  PubMed  Google Scholar 

  • Pilling D, Buckley CD, Salmon M, Gomer RH (2003) Inhibition of fibrocyte differentiation by serum amyloid P. J Immunol 171(10):5537–5546

    CAS  PubMed  Google Scholar 

  • Pilling D, Roife D, Wang M, Ronkainen SD, Crawford JR, Travis EL, Gomer RH (2007) Reduction of bleomycin-induced pulmonary fibrosis by serum amyloid P. J Immunol 179(6):4035–4044

    CAS  PubMed  Google Scholar 

  • Pilling D, Fan T, Huang D, Kaul B, Gomer RH (2009) Identification of markers that distinguish monocyte-derived fibrocytes from monocytes, macrophages, and fibroblasts. PLoS One 4(10):e7475. doi:10.1371/journal.pone.0007475

    PubMed Central  PubMed  Google Scholar 

  • Price LC, Wort SJ, Perros F, Dorfmuller P, Huertas A, Montani D, Cohen-Kaminsky S, Humbert M (2012) Inflammation in pulmonary arterial hypertension. Chest 141(1):210–221. doi:10.1378/chest.11-0793

    CAS  PubMed  Google Scholar 

  • Pu J, Gu S, Liu S, Zhu S, Wilson D, Siegfried JM, Gur D (2012) CT based computerized identification and analysis of human airways: a review. Med Phys 39(5):2603–2616. doi:10.1118/1.4703901

    PubMed Central  PubMed  Google Scholar 

  • Quan TE, Cowper S, Wu S-P, Bockenstedt LK, Bucala R (2004) Circulating fibrocytes: collagen-secreting cells of the peripheral blood. Int J Biochem Cell Biol 36(4):598–606

    CAS  PubMed  Google Scholar 

  • Reilkoff RA, Bucala R, Herzog EL (2011) Fibrocytes: emerging effector cells in chronic inflammation. Nat Rev Immunol 11(6):427–435

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ryan J, Bloch K, Archer SL (2011) Rodent models of pulmonary hypertension: harmonisation with the world health organisation’s categorisation of human PH. Int J Clin Pract Suppl 172:15–34. doi:10.1111/j.1742-1241.2011.02710.x

    PubMed  Google Scholar 

  • Salvato G (2001) Quantitative and morphological analysis of the vascular bed in bronchial biopsy specimens from asthmatic and non-asthmatic subjects. Thorax 56(12):902–906

    PubMed Central  CAS  PubMed  Google Scholar 

  • Schmidt M, Sun G, Stacey MA, Mori L, Mattoli S (2003) Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma. J Immunol 171(1):380–389

    CAS  PubMed  Google Scholar 

  • Seferian A, Simonneau G (2013) Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow? Eur Respir Rev 22(129):217–226. doi:10.1183/09059180.00001713

    PubMed  Google Scholar 

  • Seferian A, Chaumais MC, Savale L, Gunther S, Tubert-Bitter P, Humbert M, Montani D (2013) Drugs induced pulmonary arterial hypertension. Presse Med 42(9 Pt 2):e303–e310. doi:10.1016/j.lpm.2013.07.005

    PubMed  Google Scholar 

  • Shimoda LA, Laurie SS (2013) Vascular remodeling in pulmonary hypertension. J Mol Med 91(3):297–309. doi:10.1007/s00109-013-0998-0

    PubMed Central  CAS  PubMed  Google Scholar 

  • Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing ZC, Krowka MJ, Langleben D, Nakanishi N, Souza R (2009) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54(1 Suppl):S43–S54. doi:10.1016/j.jacc.2009.04.012

    PubMed  Google Scholar 

  • Spees JL, Whitney MJ, Sullivan DE, Lasky JA, Laboy M, Ylostalo J, Prockop DJ (2008) Bone marrow progenitor cells contribute to repair and remodeling of the lung and heart in a rat model of progressive pulmonary hypertension. FASEB J 22(4):1226–1236. doi:10.1096/fj.07-8076com

    CAS  PubMed  Google Scholar 

  • Stacher E, Graham BB, Hunt JM, Gandjeva A, Groshong SD, McLaughlin VV, Jessup M, Grizzle WE, Aldred MA, Cool CD, Tuder RM (2012) Modern age pathology of pulmonary arterial hypertension. Am J Respir Crit Care Med 186(3):261–272. doi:10.1164/rccm.201201-0164OC

    PubMed Central  PubMed  Google Scholar 

  • Stirling G, Kakkar V (1969) Cells in the circulating blood capable of producing connective tissue. Br J Exp Pathol 50(1):51

    PubMed Central  CAS  PubMed  Google Scholar 

  • Suga H, Rennert RC, Rodrigues M, Sorkin M, Glotzbach JP, Januszyk M, Fujiwara T, Longaker MT, Gurtner GC (2014) Tracking the elusive fibrocyte: Identification and characterization of collagen producing hematopoietic lineage cells during murine wound healing. Stem Cells 32(5):1347–1360

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tam A, Sin DD (2012) Pathobiologic mechanisms of chronic obstructive pulmonary disease. Med Clin North Am 96(4):681–698. doi:10.1016/j.mcna.2012.04.012

    CAS  PubMed  Google Scholar 

  • Tamosiuniene R, Tian W, Dhillon G, Wang L, Sung YK, Gera L, Patterson AJ, Agrawal R, Rabinovitch M, Ambler K, Long CS, Voelkel NF, Nicolls MR (2011) Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension. Circ Res 109(8):867–879. doi:10.1161/CIRCRESAHA.110.236927

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tervaert JW, Limburg PC, Elema JD, Huitema MG, Horst G, The TH, Kallenberg CG (1991) Detection of autoantibodies against myeloid lysosomal enzymes: a useful adjunct to classification of patients with biopsy-proven necrotizing arteritis. Am J Med 91(1):59–66

    CAS  PubMed  Google Scholar 

  • Tuder RM, Archer SL, Dorfmuller P, Erzurum SC, Guignabert C, Michelakis E, Rabinovitch M, Schermuly R, Stenmark KR, Morrell NW (2013) Relevant issues in the pathology and pathobiology of pulmonary hypertension. J Am Coll Cardiol 62(25 Suppl):D4–D12. doi:10.1016/j.jacc.2013.10.025

    PubMed Central  PubMed  Google Scholar 

  • Ushiki T (2002) Collagen fibers, reticular fibers and elastic fibers. A comprehensive understanding from a morphological viewpoint. Arch Histol Cytol 65(2):109–126

    PubMed  Google Scholar 

  • Wang X, Zhu H, Yang X, Bi Y, Cui S (2010) Vasohibin attenuates bleomycin induced pulmonary fibrosis via inhibition of angiogenesis in mice. Pathology 42(5):457–462. doi:10.3109/00313025.2010.493864

    CAS  PubMed  Google Scholar 

  • Wansleeben C, Barkauskas CE, Rock JR, Hogan BL (2013) Stem cells of the adult lung: their development and role in homeostasis, regeneration, and disease. Wiley Interdiscip Rev Dev Biol 2(1):131–148. doi:10.1002/wdev.58

    CAS  PubMed  Google Scholar 

  • Weiss DJ, Kolls JK, Ortiz LA, Panoskaltsis-Mortari A, Prockop DJ (2008) Stem cells and cell therapies in lung biology and lung diseases. Proc Am Thorac Soc 5(5):637–667. doi:10.1513/pats.200804-037DW

    PubMed Central  PubMed  Google Scholar 

  • Wienke D, MacFadyen JR, Isacke CM (2003) Identification and characterization of the endocytic transmembrane glycoprotein Endo180 as a novel collagen receptor. Mol Biol Cell 14(9):3592–3604

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wright JL, Petty T, Thurlbeck WM (1992) Analysis of the structure of the muscular pulmonary arteries in patients with pulmonary hypertension and COPD: National Institutes of Health nocturnal oxygen therapy trial. Lung 170(2):109–124

    CAS  PubMed  Google Scholar 

  • Wu YJ, La Pierre DP, Jin W, Albert JY, Burton BY (2005) The interaction of versican with its binding partners. Cell Res 15(7):483–494

    CAS  PubMed  Google Scholar 

  • Zambidis ET, Peault B, Park TS, Bunz F, Civin CI (2005) Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development. Blood 106(3):860–870

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zanini A, Chetta A, Olivieri D (2008) Therapeutic perspectives in bronchial vascular remodeling in COPD. Ther Adv Respir Dis 2(3):179–187. doi:10.1177/1753465808092339

    PubMed  Google Scholar 

  • Zhang W, Chuang Y-J, Swanson R, Li J, Seo K, Leung L, Lau LF, Olson ST (2004) Antiangiogenic antithrombin down-regulates the expression of the proangiogenic heparan sulfate proteoglycan, perlecan, in endothelial cells. Blood 103(4):1185–1191

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics-Critical Care, University of Colorado Denver, Aurora, CO, 80045, USA

    Kelley L. Colvin & Michael E. Yeager

  2. Cardiovascular Pulmonary Research, University of Colorado Denver, Aurora, CO, 80045, USA

    Kelley L. Colvin & Michael E. Yeager

  3. Department of Bioengineering, University of Colorado Denver, Aurora, CO, 80045, USA

    Kelley L. Colvin & Michael E. Yeager

  4. Linda Crnic Institute for Down Syndrome, University of Colorado Denver, Aurora, CO, 80045, USA

    Kelley L. Colvin & Michael E. Yeager

  5. Department of Bioengineering, University of Colorado Denver, Aurora, CO, 80045, USA

    Ozus Lohani

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  1. Kelley L. Colvin
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  2. Ozus Lohani
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  3. Michael E. Yeager
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Correspondence to Michael E. Yeager .

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  1. Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, USA

    Amy Firth

  2. Department of Medicine, The Univsersity of Arizona, Tucson, Arizona, USA

    Jason X.-J. Yuan

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Colvin, K.L., Lohani, O., Yeager, M.E. (2015). Fibrocytes and Pulmonary Vascular Remodeling: The Good, the Bad, and the Progenitors. In: Firth, A., Yuan, JJ. (eds) Lung Stem Cells in the Epithelium and Vasculature. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-16232-4_14

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