Abstract
Human sepsis is a spectrum of pathophysiological changes in the host system resulting from a generalized activation and systemic expression of the host’s inflammatory pathways in response to infection. The endothelium plays a key role in the pathogenesis of sepsis, and studies of endothelial derangement and its underlying pathophysiological mechanisms in sepsis have become of considerable interest in both the clinical and pathological fields. Recognition, as well as contact formation, between leukocytes and the endothelium is dependent on the presence of both cytokines and adhesion molecules that mediate leukocyte-endothelial cell adhesive interactions. The adherence of leukocytes on the vascular endothelial cell surface and the transmigration through the endothelial layer is regulated by at least three adhesion molecule families: the selectins (E-Selectin, L-Selectin, P-Selectin), the integrins (e.g., lymphocyte function-associated antigen-1, Mac-1, very late activation antigen-4), and the immunoglobulin superfamily (e.g., intercellular adhesion molecule-1, vascular cell adhesion molecule-1). The constitutively expressed platelet endothelial cell adhesion molecule-1, already strongly expressed by endothelial cells lacking inflammatory stimuli, is localized at the cell-to-cell borders of endothelial cells and mediates a common final step in the extravasation of monocytes and neu-trophils during the inflammatory response from the vascular lumen through the endothelium. In addition, platelet-activating factor, released in response to endotoxin, is another mediator of considerable relevance for endotoxin-induced leukocyte recruitment into tissue in sepsis, leading to loss of fluid from the intravascular into the extravascular space, thus contributing to the progressive loss of circulating blood and, thereby, to a depression of cardiac output. Studies have demonstrated that this loss of fluid is not the result of changes in hydrostatic and/or osmotic pressures within the vascular compartment, but rather thebreakdown of endothelial barrier function, thus allowing emigration of fluid and macromolecules—including proteins—into the extravascular space. Separation of tight junctions between endothelial cells, influenced by inflammatory mediators and white blood cells, and dysfunction rather than destructive changes of endothelial cells leading to defects in endothelial cell volume regulation are discussed as the main underlying pathophysiological mechanisms. Two major pathways are involved in initiation of apoptosis in sepsis: a receptor-initiated caspase-8-mediated pathway and a mitochondrial-initiated caspase-9-mediated pathway. In vitro studies have revealed apoptotic cell death of endothelial cells in response to LPS and tumor necrosis factor-α, as well as to certain microorganisms. A number of studies suggest that endotoxin induces expression of antiapoptotic molecules in microvascular endothelial cells and neutrophils. The latter could play a role in the accumulation of neutrophils during sepsis, as well as in prolongation and/or augmentation of the inflammatory response.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP (1995) The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 273, 117–123.
Torpy JM (2002) New threats and old enemies: challenges for critical care medicine. JAMA 287, 1513–1515.
Baumgartner JD, Calandra T (1999) Treatment of sepsis: past and future avenues. Drugs 57, 127–132.
Ivanov AI, Patel S, Kulchitsky VA, Romanovsky AA (2003) Platelet-activating factor: a previously unrecognized mediator of fever. J Physiol 553, 221–228.
Kox WJ, Volk T, Kox SN, Volk HD (2000) Immunomodulatory therapies in sepsis. Intensive Care Med 26(Suppl 1), S124–S128.
Godshall CJ, Scott MJ, Burch PT, Peyton JC, Cheadle WG (2003) Natural killer cells participate in bacterial clearance during septic peritonitis through interactions with macrophages. Shock 19, 144–149.
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference (1992) Definition for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20, 864–874.
Ayres SM (1985) SCCM’s new horizons conference on sepsis and septic shock. Crit Care Med 13, 864–866.
Balk RA, Bone RC (1989) The septic syndrome. Definition and clinical implications. Crit Care Clin 5, 1–8.
Adrie C, Pinsky MR (2000) The inflammatory balance in human sepsis. Intensive Care Med 26, 364–375.
Hack CE, Zeerleder S (2001) The endothelium in sepsis: source of and a target for inflammation. Crit Care Med 29(Suppl 7), S21–S27.
Bone RC (1994) Sepsis and SIRS. Nephrol Dial Transplant 9(Suppl 4), 99–103.
Bone RC (1994) Sepsis and its complications: the clinical problem. Crit Care Med 22, 8–11.
Weigand MA, Horner C, Bardenheuer HJ, Bouchon A (2004) The systemic inflammatory response syndrome. Best Pract Res Clin Anaesthesiol 18, 455–475.
Larmann J, Theilmeier G. Inflammatory response to cardiac surgery: cardiopul-monary bypass versus non-cardiopulmonary bypass surgery (2004) Best Pract Res Clin Anaesthesiol 18, 425–438.
Singer M, De Santis V, Vitale D, Jeffcoate W (2004) Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet 364, 545–548.
Bone RC (1996) Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 24, 1125–1128.
Bone RC (1996) Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS). Ann Intern Med 125, 680–687.
Ebnet K, Vestweber D (1999) Molecular mechanisms that control leukocyte extravasation: the selectins and the chemokines. Histochem Cell Biol 112, 1–23.
Czermak BJ, Breckwoldt M, Ravage ZB, et al. (1999) Mechanisms of enhanced lung injury during sepsis. Am J Pathol 154, 1057–1065.
Kaplan RL, Sahn SA, Petty TL (1979) Incidence and outcome of respiratory distress syndrome in gram-negative sepsis. Arch Intern Med 139, 867–869.
Weiland JE, Davis WB, Holter JF, Mohammed JR, Dorinsky PM, Gadek JE (1986) Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. Am Rev Respir Dis 133, 218–225.
Ertel W, Morrison MH, Wang P, Zheng F, Ayala A, Chaudry ICH (1991) The complex patterns of cytokines in sepsis. Ann Surg 214, 141–148.
Thijs LG, Hack CE (1995) Time course of cytokine levels in sepsis. Intensive Care Med 21, 258–263.
Tracey KJ, Lowry SF (1990) The role of cytokine mediators in septic shock. Adv Surg 23, 21–56.
Walley KR, Lukacs NW, Standiford TJ, Strieter RM, Kunkel SL (1996) Balance of inflammatory cytokines related to severity and mortality of murine sepsis. Infect Immun 64, 4733–4738.
Wichtermann KA, Bauer AE, Chaudry ICH (1980) Sepsis and shock: a review of laboratory models and a proposal. J Surg Res 29, 189–201.
Bevilacqua MP, Pober JS, Wheeler ME, Cotran RS, Gimbrone MA (1985) Inter-leukin 1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion. Am J Pathol 121, 393–403.
Pober JS (1988) Cytokine-mediated activation of vascular endothelium. Am J Pathol 133, 426–433.
Strieter RM, Kunkel SL (1994) Acute lung injury: the role of cytokines in the elic-itation of neutrophils. Journal Invest Med 42, 640–651.
Butcher EC (1991) Leukocyte-endothelial cell recognition: three (ore more) steps to specifity and diversity. Cell 67, 1033–1036.
Carlos TM, Harlan JM (1994) Leukocyte-endothelial adhesion molecules. Blood 84, 2068–2101.
Osborn L (1990) Leukocyte adhesion to endothelium in inflammation. Cell 62, 3–6.
Lukacs NW, Ward PA (1996) Inflammatory mediators, cytokines, and adhesion molecules in pulmonary inflammation and injury. Adv Immunol 62, 257–304.
Springer TA (1990) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76, 301–314.
Tomczok J, Sliwa-Tomczok W, Klein CL, Bittinger F, Kirkpatrick CJ (1994) Application of immunogold labeling for light and electron microscopic localization of endothelial leukocyte adhesion molecule 1 (ELAM-1) on cultured human endothelial cells. Micron 25, 257–266.
Kapiotis S, Quehenberger P, Sengoelge G, Partan C, Eher R, Strobl H, et al. (1994) Modulation of pyrogen-induced upregulation of endothelial cell adhesion molecules (CAMs) by interleukin-4: transcriptional mechanisms and CAM-shedding. Circ Shock 43, 18–25.
Chuang PI, Young BA, Thiagarajan RR, Cornejo C, Winn RK, Harlan JM (1997) Cytoplasmic domain of E-selectin contains a non-tyrosine endocytosis signal. J Biol Chem 272, 24,813–24,818.
Fries JWU, Williams AJ, Atkins RC, Newman W, Lipscomb MF, Collins T (1993) Expression of VCAM-1 and E-selectin in an in vivo model of endothelial activation. Am J Pathol 143, 725–737.
Müller AM, Cronen C, Müller KM, Kirkpatrick C (1999) Comparative analysis of the reactivity of human umbilical vein endothelial cells in organ and monolayer culture. Pathobiology 67, 99–107.
Redl H, Dinges HP, Buurman WA, van der Linden CJ, Pober JS, Cotran RS, et al. (1991) Expression of endothelial leukocyte adhesion molecule-1 in septic but not traumatic/hypovolemic shock in the baboon. Am J Pathol 139, 461–466.
Ishii H, Majerus PW (1985) Thrombomodulin is present in human plasma and urine. J Clin Invest 76, 2178–2181.
Patrick D, Betts J, Frey EA, Prameya R, Dorovini-Zis K, Finlay BB (1992) Haemophilus influenzae lipopolysaccharide disrupts confluent monolayers of bovine brain endothelial cells via a serum-dependent cytotoxic pathway. J Infect Dis 165, 865–872.
Gearing AJ, Newman W (1993) Circulating adhesion molecules in disease. Immunol Today 14, 506–512.
Myers CL, Wertheimer SJ, Schembri-King J, Parks T, Wallace RW (1992) Induction of ICAM-1 by TNF-alpha, IL-1 beta, and LPS in human endothelial cells after downregulation of PKC. Am J Physiol 263, C767–C772.
Javaid K, Rahman A, Anwar KN, Frey RS, Minshall RD, Malik AB (2003) Tumor necrosis factor-alpha induces early-onset endothelial adhesivity by protein kinase Czeta-dependent activation of intercellular adhesion molecule-1. Circ Res 92, 1089–1097.
Raab M, Daxecker H, Markovic S, Karimi A, Griesmacher A, Mueller MM (2002) Variation of adhesion molecule expression on human umbilical vein endothelial cells upon multiple cytokine application. Clin Chim Acta 321, 11–16.
van der Poll T, Coyle SM, Levi M, et al. (1997) Effect of a recombinant dimeric tumor necrosis factor receptor on inflammatory responses to intravenous endo-toxin in normal humans. Blood 89, 3727–3734.
Collins T, Read MA, Neish AS, Whithley MZ, Thanos D, Maniatis T (1995) Tran-scriptional regulation of endothelial cell adhesion molecules: NF-κB and cytokine-nducible enhancers. FASEB 9, 899–909.
Patel KD, Cuvelier SL, Wiehler S (2002) Selectins: critical mediators of leukocyte recruitment. Semin Immunol 14, 73–81.
Müller AM, Cronen C, Müller KM, Kirkpatrick CJ (2002) Heterogeneous expression of cell adhesion molecules by endothelial cells in ARDS. J Pathol 198, 270–275.
Klein CL, Köhler H, Bittinger F, et al. (1994) Comparative studies on vascular endothelium in vitro. I: Cytokine effects on the expression of adhesion molecules by human umbilical vein, saphenous vein and femoral artery endothelial cells. Pathobiology 62, 199–208.
Adamson P, Tighe M, Pearson JD (1996) Protein tyrosine kinase inhibitors act downstream of IL-1 alpha and LPS stimulated MAP-kinase phosphorylation to inhibit expression of E-selectin on human umbilical vein endothelial cells. Cell Adhes Commun 3, 511–525.
Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76, 301–314.
Kuhns DB, Alvord WG, Gallin JI (1995) Increased circulating cytokines, cytokine antagonists, and E-selectin after intravenous administration of endotoxin in humans. J Infect Dis 171, 145–152.
Huang K, Fishwild DM, Wu HM, Dedrick RL (1995) Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein. Inflammation 19, 389–404.
Tsokos M, Fehlauer F, Püschel K (2000) Immunohistochemical expression of e-selectin in sepsis-induced lung injury. Int J Legal Med 13, 338–342.
Bevilacqua MP (1993) Endothelial-leukocyte adhesion molecules. Annu Rev Immunol 11, 767–804.
Klein CL, Bittinger F, Köhler H, et al. (1995) Comparative studies on vascular endothelium in vitro. Effects of cytokines on the expression of E-selectin, ICAM-1 and VCAM by cultured human endothelial cells obtained from different passages. Pathobiology 63, 83–92.
Parrillo JE (1993) Pathogenetic mechanisms of septic shock. N Engl J Med 328, 1471–1477.
Bone RC (1991) The pathogenesis of sepsis. Ann Intern Med 115, 457–469.
Tsouknos A, Nash GB, Rainger GE (2003) Monocytes initiate a cycle of leukocyte recruitment when cocultured with endothelial cells. Atherosclerosis 170, 49–58.
Müller AM, Cronen C, Kupferwasser LI, Oelert H, Müller KM, Kirkpatrick CJ (2000) Expression of endothelial cell adhesion molecules on heart valves: upreg-ulation in degeneration as well as acute endocarditis. J Pathol 191, 54–60.
Heckmann M, Douwes K, Peter R, Degitz K (1998) Vascular activation of adhesion molecule mRNA and cell surface expression by ionizing radiation. Exp Cell Res 238, 148–154.
Combe C, Dupla C, Couffinhal T, Moreau C, Bonnet J (1995) Induction of intercellular adhesion molecule-1 by monocyte adhesion to endothelial cells in human culture system. J Cell Physiol 164, 295–303.
Drake TA, Cheng J, Chang A, Taylor FB Jr (1993) Expression of tissue factor, thrombomodulin and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Pathol 142, 1458–1470.
Kayal S, Jaïs J-P, Aguini N, Chaudire J, Labrousse J (1998) Elevated circulating E-selectin, intercellular adhesion molecule 1, and von Willebrand factor in patients with severe infection. Am J Respir Crit Care Med 157, 776–784.
Peters K, Unger RE, Brunner J, Kirkpatrick CJ (2003) Molecular basis of endothelial dysfunction in sepsis. Cardiovasc Res 60, 49–57.
Simmons DL, Walker C, Power C, Pigott R (1990) Molecular cloning of CD 31, a putative intercellular adhesion molecule closely related to carcinoembronic antigen. J Exp Med 171, 2147–2152.
DeLisser HM, Chilkotowsky J, Yan HC, Daise ML, Buck CA, Albelda SM (1994) Deletions in the cytoplasmic domain of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD 31) result in changes in ligand binding properties. J Cell Biol 124, 195–203.
Bogen S, Pak J, Garifallou M, Deng X, Müller WA (1994) Monoclonal antibody to murine PECAM-1 (CD 31) blocks acute inflammation in vivo. J Exp Med 1779, 1059–1064.
Gibbs P, Berkley LM, Bolton EM, Briggs JD, Bradley JA (1993) Adhesion molecule expression (ICAM-1, VCAM-1, E-selectin and PECAM) in human kidney allografts. Transpl Immunol 1, 109–113.
Wong D, Dorovini-Zis K (1996) Platelet endothelial cell adhesion molecule-1 (PECAM-1) expression by human brain microvessel endothelial cells in primary culture. Brain Res 731, 217–220.
Henninger DD, Panes J, Eppihimer M, et al. (1997) Cytokine-induced VCAM-1 and ICAM-1 expression in different organs of the mouse. J Immunol 158, 1825–1832.
Romer LH, McLean NV, Yan HC, Daise M, Sun J, DeLisser HM (1995) IFN-gamma and TNF-alpha induce redistribution of PECAM-1 (CD 31) on human endothelial cells. J Immunol 154, 6582–6592.
Stewart RJ, Kashxur TS, Marsden PA (1996) Vascular endothelial platelet endothelial adhesion molecule-1 (PECAM-1) expression is decreased by TNF-alpha and IFN-gamma. Evidence for cytokine-induced destabilization of messenger ribonucleic acid transcipts in bovine endothelial cells. J Immunol 156, 1221–1228.
Gurubhagavatula I, Amrani Y, Pratico D, Ruberg FL, Albelda SM, Panettieri RA Jr (1998) Engagement of human PECAM-1 (CD31) on human endothelial cells increases intracellular calcium ion concentration and stimulates prostacyclin release. J Clin Invest 101, 212–222.
Cuschieri J, Gourlay D, Garcia I, Jelacic S, Maier RV (2003) Modulation of endo-toxin-induced endothelial function by calcium/calmodulin-dependent protein kinase. Shock 20, 176–182.
Schumann RR, Leong SR, Flaggs GW, Gray PW, Wright SD, Mathison JC, et al. (1990) Structure and function of lipopolysaccharide binding protein. Science 249, 1429–1431
El-Samalouti VT, Schletter J, Brade H, et al. (1997) Detection of lipopolysaccharide (LPS)-binding membrane proteins by immuno-coprecipitation with LPS and anti-LPS antibodies. Eur J Biochem 250, 418–424.
Fan X, Stelter F, Menzel R, et al. (1999) Structures in Bacillus subtilis are recognized by CD14 in a lipopolysaccharide binding protein-dependent reaction. Infect Immun 67, 2964–2968.
Faure E, Equils O, Sieling PA, et al. (2000) Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem. 275, 11058–11063.
Faure E, Thomas L, Xu H, Medvedev A, Equils O, Arditi M (2001) Bacterial lipopolysaccharide and IFN-gamma induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial cells: role of NF-kappa B activation. J Immunol 166, 2018–2024.
Beutler B (2000) Tlr4: central component of the sole mammalian LPS sensor. Curr Opin Immunol 12, 20–26.
Underhill DM, Ozinsky A, Smith KD, Aderem A (1999) Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci USA 96, 14,459–14,463.
Reiling N, Holscher C, Fehrenbach A, et al. (2002) Cutting edge: Toll-like receptor (TLR)2-and TLR4-mediated pathogen recognition in resistance to airborne infection with Mycobacterium tuberculosis. J Immunol 169, 3480–3484.
Hayashi F, Smith KD, Ozinsky A, et al. (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099–1103.
Hemmi H, Takeuchi O, Kawai T, et al. (2000) Toll-like receptor recognizes bacterial DNA. Nature 408, 740–745.
Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413, 732–738.
Hirschfeld M, Ma Y, Weis JH, Vogel SN, Weis JJ (2000) Cutting edge: repurifica-tion of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J Immunol 165, 618–622.
Song GY, Chung CS, Jarrar D, Cioffi WG, Ayala A (2002) Mechanism of immune dysfunction in sepsis: inducible nitric oxide-meditated alterations in p38 MAPK activation. J Trauma 53, 276–282.
Tamura DY, Moore EE, Johnson JL, Zallen G, Aiboshi J, Silliman CC (1998) p38 mitogen-activated protein kinase inhibition attenuates intercellular adhesion molecule-1 up-regulation on human pulmonary micro vascular endothelial cells. Surgery 124, 403–407.
Liu SF, Ye X, Malik AB (1999) Pyrrolidine dithiocarbamate prevents I-kappaB degradation and reduces microvascular injury induced by lipopolysaccharide in multiple organs. Mol Pharmacol 55, 658–667.
Wagner M, Klein CL, van Kooten TG, Kirkpatrick CJ (1998) Mechanisms of cell activation by heavy metal ions. J Biomed Mater Res 42, 443–452.
Moll T, Czyz M, Holzmuller H, et al. (1995) Regulation of the tissue factor promoter in endothelial cells. Binding of NF kappa B-, AP-1-, and Sp1-like transcription factors. J Biol Chem 270, 3849–3857.
Whiteside ST, Israel A (1997) I kappa B proteins: structure, function and regulation. Semin Cancer Biol 8, 75–82.
Kirkpatrick CJ, Bittinger F, Klein CL, Hauptmann S, Klosterhalfen B (1996) The role of the microcirculation in multiple organ dysfunction syndrome (MODS): a review and perspective. Virchows Arch 427, 461–476.
Anderson BO, Bensard DD, Harken AH (1991) The role of platelet activating factor and its antagonists in shock, sepsis and multiple organ failure. Surg Gynecol Obstet 172, 415–424.
Schmidt W, Stenzel K, Gebhard MM, Martin E, Schmidt H (1999) C1-esterase inhibitor and its effects on endotoxin-induced leukocyte adherence and plasma extravasation in postcapillary venules. Surgery 125, 280–287.
Eichhorn ME, Ney L, Suchner U, Goetz AE (1999) Impact of arachidonic acid on microhemodynamics and leukocyte adhesion in alveolar capillaries during endo-toxemia. Langenbecks Arch Chir I 115, 493–497.
Chien S, Chang C, Dellenback RJ, Usami S, Gregersen MI (1966) Hemodynamic changes in endotoxin shock. Am J Physiol 210, 1401–1410.
Solomon LA, Hinshaw LB (1968) Effect of endotoxin on isogravimetric capillary pressure in the forelimb. Am J Physiol 214, 443–447.
Blum MS, Toninelli E, Anderson JM, et al. (1997) Cytoskeletal rearrangement mediates human microvascular endothelial tight junction modulation by cytokines. Am J Physiol 273, H286–294.
Bannerman DD, Fitzpatrick MJ, Anderson DY, et al. (1998) Endotoxin-neutraliz-ing protein protects against endotoxin-induced endothelial barrier dysfunction. Infect Immun 66, 1400–1407.
Carden DL, Granger DN (2000) Pathophysiology of ischaemia-reperfusion injury. J Pathol 190, 255–266.
Voss BL, De Bault LE, Blick KE, et al. (1991) Sequential renal alterations in septic shock in the primate. Circ Shock 33, 142–155.
Rafi AQ, Zeytun A, Bradley MJ, et al. (1998) Evidence for the involvement of Fas ligand and perforin in the induction of vascular leak syndrome. J Immunol 161, 3077–3086.
Bannerman DD, Sathyamoorthy M, Goldblum SE (1998) Bacterial lipopolysac-charide disrupts endothelial monolayer integrity and survival signaling events through caspase cleavage of adherens junction proteins. J Biol Chem 273, 35,371–35,380.
Gross PL, Aird WC (2000) The endothelium and thrombosis. Semin Thromb Hemost 26, 463–478.
Rosenberg RD, Aird WC (1999) Vascular bed-specific hemostasis and hypercoag-ulable states. N Engl J Med 340, 1555–1564.
Aird WC (2001) Vascular bed-specific hemostasis: role of endothelium in sepsis pathogenesis. Crit Care Med 29, S28–34.
Aird WC (2002) Endothelial cell dynamics and complexity theory. Crit Care Med 30,5 Suppl.: S180–S185.
Müller AM, Skrzynski C, Skipka G, Müller KM (2002) Expression of von Wille-brand factor by human pulmonary endothelial cells in vivo. Respiration 69, 526–533.
Müller AM, Nesslinger M, Skipka G, Müller KM (2002) Expression of CD34 in pulmonary endothelial cells in vivo. Pathobiology 70, 11–17.
Iskit AB, Sungur A, Gedikoglu G, Guc MO (1999) The effects of bosentan, aminoguanidine and L-canavanine on mesenteric blood flow, spleen and liver in endotoxaemic mice. Eur J Pharmacol 379, 73–80.
Kavuklu B, Iskit AB, Guc MO, Ilhan M, Sayek I (2000) Aminoguanidine attenuates endotoxin-induced mesenteric vascular hyporeactivity. Br J Surg 87, 448–453
Baykal A, Kavuklu B, Iskit AB, Guc MO, Hascelik G, Sayek I (2000) Experimental study of the effect of nitric oxide inhibition on mesenteric blood flow and inter-leukin-10 levels with a lipopolysaccharide challenge. World J Surg 24, 1116–1120.
Baykal A, Iskit AB, Hamaloglu E, Oguz Guc M, Hascelik G, Sayek I (2000) Mela-tonin modulates mesenteric blood flow and TNFalpha concentrations after lipopolysaccharide challenge. Eur J Surg 166, 722–727.
Kubli S, Boegli Y, Ave AD, et al. (2003) Endothelium-dependent vasodilation in the skin microcirculation of patients with septic shock. Shock 19, 274–280.
Feuerhake F, Fuchsl G, Bals R, Welsch U (1998) Expression of inducible cell adhesion molecules in the normal human lung: immunohistochemical study of their distribution in pulmonary blood vessels. Histochem Cell Biol 110, 387–394.
Eppihimer MJ, Wolitzky B, Anderson DC, Labow MA, Granger DN (1996) Heterogeneity of expression of e-and P-selectins in vivo. Circ Res 79, 560–569.
Doerschuk CM, Beyers N, Coxson HO, Wiggs BR, Hogg JC (1993) The importance of neutrophil and capillary diameter in the margination of PMN in the lung. J Appl Physiol 74, 3040–3045.
Pearson JD (1999) Endothelial cell function and thrombosis. Baillieres Best Pract Res Clin Haematol 12, 329–341.
Yamamoto K, Loskutoff DJ (1996) Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator. J Clin Invest 97, 2440–2451.
Farquhar I, Martin CM, Lam C, Potter R, Ellis CG, Sibbald WJ (1996) Decreased capillary density in vivo in bowel mucosa of rats with normotensive sepsis. J Surg Res 61, 190–196.
Yan SF, Tritto I, Pinsky D, et al. (1995) Induction of interleukin 6 (IL-6) by hypoxia in vascular cells. Central role of the binding site for nuclear factor-IL-6. J Biol Chem 270, 11,463–11,471.
Caplan MS, Adler L, Kelly A, Hsueh W (1992) Hypoxia increases stimulus-induced PAF production and release from human umbilical vein endothelial cells. Biochim Biophys Acta 1128, 205–210.
Ogawa S, Shreeniwas R, Brett J, Clauss M, Furie M, Stern DM (1990) The effect of hypoxia on capillary endothelial cell function: modulation of barrier and coagulant function. Br J Haematol 75, 517–524.
Yamamoto K, de Waard V, Fearns C, Loskutoff DJ (1998) Tissue distribution and regulation of murine von Willebrand factor gene expression in vivo. Blood 92, 2791–2801.
Thiemermann C, Vane J (1990) Inhibition of nitric oxide synthesis reduces the hypotension induced by bacterial lipopolysaccharides in the rat in vivo. Eur J Pharmacol 182, 591–595.
Julou-Schaeffer G, Gray GA, Fleming I, Schott C, Parratt JR, Stoclet JC (1990) Loss of vascular responsiveness induced by endotoxin involves L-arginine pathway. Am J Physiol 259, H1038–1043.
Guc MO, Furman BL, Parratt JR (1990) Endotoxin-induced impairment of vaso-pressor and vasodepressor responses in the pithed rat. Br J Pharmacol 101, 913–919
Kilbourn RG (1998) The discovery of nitric oxide as a key mediator in septic shock. Sepsis 1, 85–91.
Hu X, Yee E, Harlan JM, Wong F, Karsan A (1998) Lipopolysaccharide induces the antiapoptotic molecules, A1 and A20, in micro vascular endothelial cells. Blood 92, 2759–2765.
Roy S, Nicholson DW (2000) Cross-talk in cell death signaling. J Exp Med 192, F21–25.
Robaye B, Mosselmans R, Fiers W, Dumont JE, Galand P (1991) Tumor necrosis factor induces apoptosis (programmed cell death) in normal endothelial cells in vitro. Am J Pathol 138, 447–453.
Frey EA, Finlay BB (1998) Lipopolysaccharide induces apoptosis in a bovine endothelial cell line via a soluble CD 14 dependent pathway. Microb Pathog 24, 101–109.
Sylte MJ, Corbeil LB, Inzana TJ, Czuprynski CJ (2001) Haemophilus somnus induces apoptosis in bovine endothelial cells in vitro. Infect Immun 69, 1650–1660.
Menzies BE, Kourteva I (1998) Internalization of Staphylococcus aureus by endothelial cells induces apoptosis. Infect Immun 66, 5994–5998.
Harter L, Keel M, Steckholzer U, Ungethuem U, Trentz O, Ertel W (2002) Activation of mitogen-activated protein kinases during granulocyte apoptosis in patients with severe sepsis. Shock 18, 401–406.
Hotchkiss RS, Dunne WM, Swanson PE, et al. (2001) Role of apoptosis in Pseudomonas aeruginosa pneumonia. Science 294, 1783.
Tsokos M, Mack D, Püschel K (2002) Postmortale bakteriologische Diagnostik. Entnahmetechnik, Untersuchungsmaterial, limitierende Faktoren, diagnostische Wertigkeit und Interpretation. Rechtsmedizin 12, 59–64.
O’Boyle CJ, MacFie J, Mitchell CJ, Johnstone D, Sagar PM, Sedman PC (1998) Microbiology of bacterial translocation in humans. Gut 42, 29–35.
Woodcock NP, Robertson J, Morgan DR, Gregg KL, Mitchell CJ, MacFie J (2001) Bacterial translocation and immunohistochemical measurement of gut immune function. Clin Pathol 54, 619–623.
Tsokos M, Püschel K (1999) Iatrogenic Staphylococcus aureus septicaemia following intravenous and intramuscular injections: clinical course and pathomor-phological findings. Int J Legal Med 112, 303–308.
Heinemann A, Tsokos M, Püschel K (2003) Medicolegal aspects of pressure sores Leg Med 5(Suppl 1), S263–S266.
Tsokos M (2002) Pathology of sepsis. Part I: Forensic problems arising in the postmortem diagnosis of death due to sepsis. Jpn J Forens Pathol 8, 72–77.
Sperhake JP, Tsokos M (2004) Pathological features of Waterhouse-Friderichsen syndrome in infancy and childhood. In Tsokos M, ed., Forensic Pathology Reviews, Vol. 1. Humana Press, Totowa, NJ, pp. 219–231.
Dashefsky B, Teele DW, Klein JO (1983) Unsuspected meningococcemia. J Pedi-atr 102, 69–72.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Humana Press Inc., Totowa, NJ
About this chapter
Cite this chapter
Müller, A.M., Tsokos, M. (2006). Pathology of Human Endothelium in Septic Organ Failure. In: Tsokos, M. (eds) Forensic Pathology Reviews. Forensic Pathology Reviews, vol 4. Humana Press. https://doi.org/10.1007/978-1-59259-921-9_7
Download citation
DOI: https://doi.org/10.1007/978-1-59259-921-9_7
Publisher Name: Humana Press
Print ISBN: 978-1-58829-601-6
Online ISBN: 978-1-59259-921-9
eBook Packages: MedicineMedicine (R0)