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Bedeutung der Leukozyten-Endothelzell- Interaktion für die Manifestation der Leberfunktionsstörung nach Ischämie/Reperfusion und Endotoxinämie

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Forschung ohne Tierversuche 2000

Part of the book series: Ersatz- und Ergänzungsmethoden zu Tierversuchen ((TIERVERSUCHE))

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Zusammenfassung

Störungen der Mikrozirkulation sind für die Manifestation des Organschadens nach Ischämie/Reperfusion und Endotoxinämie/Sepsis von entscheidender Bedeutung. Insbesonders werden heute die Persistenz nutritiver Perfusionsstörungen mit fokaler Minderperfusion und Hypoxie vitaler Organe, einschließlich der Leber, sowie die Aktivierung zellulärer und humoraler Systeme sowohl für die Entwicklung als auch für die Progredienz des multiplen Organversagens als ursächliche Mechanismen diskutiert. Kausal wirksame Strategien zur Protektion der Leber bei Ischämie/Reperfusion und Endotoxinämie/Sepsis verlangen daher detaillierte Kenntnisse über mikrohämodynamische, zelluläre und molekulare Mechanismen, welche zur Gewebeschädigung fuhren bzw. diese vermitteln. In vivo-Untersuchungen der hepatischen Mikrozirkulation mittels Fluoreszenzmikroskopie erlauben aufgrund der simultanen Erfassung von nutritiver Perfusion, Zell-Zell-Interaktion, Zellfunktion und - integrität aus in vitro-Untersuchungen erzielte Ergebnisse hinsichtlich ihrer funktionellen Bedeutung für die Manifestation des Gewebeschadens zu überprüfen. Inwieweit die im Experiment nachgewiesene Effektivität dieser therapeutischen Interventionen für die Klinik Gültigkeit hat, muß in prospektiv randomisierten Studien geprüft werden.

Summary

Microcirculatory disturbances play a pivotal role for the manifestation of organ injury following ischemia/reperfusion and endotoxemia/sepsis. Persistence of nutritive perfusion failure, local ischemia and hypoxia of vital organs, including the liver, as well as the activation of cellular and humoral systems are considered as causative mechanisms for both the initiation and the propagation of multiple organ failure. Therapeutic strategies aiming at protection of liver tissue should be based upon detailed information on microvascular, cellular and molecular mechanisms leading to organ damage. Simultaneous assessment of nutritive perfusion, cell-cell interaction, parenchymal cell function and integrity by means of In vivo fluorescence microscopy of the hepatic microcirculation allows to prove the functional role of proposed mechanisms deduced from in vitro studies. Final efffectiveness of experimentally proved therapeutic regimen has to be analyzed in subsequent randomized, prospective clinical trials.

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Literatur

  • Bader A., Knop E., Kern A., Boker K., Fruhauf N., Crome O., Esselmann H., Pape C., Kempka G., Sewing K.F., 3-D coculture of hepatic sinusoidal cells with primary hepatocytes - design of an organotypical model, Exp Cell Res, 226,223–233, 1996

    Article  PubMed  CAS  Google Scholar 

  • Bauer M., Pathophysiologie der Sepsis, Anaesthesist, 45, 312–322, 1996

    Article  PubMed  CAS  Google Scholar 

  • Bone RC., Immunologie dissonance: a continuing evolution in our understanding of the systemic inflammatory response Syndrome (SIRS) and the multiple organ dysfunetion Syndrome (MODS), Ann Intern Med, 125, 680–687,1996

    PubMed  CAS  Google Scholar 

  • Boyden S., The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leukocytes, J Exp Med, 115,453–466, 1962

    Article  PubMed  CAS  Google Scholar 

  • Boermeester M.A., Houdijk A.P.J., Meyer S., Cuesta M.A., Appelmelk B.J., Wesdorp R.I.C., Hack C.E., Van Leeuwen P.A.M., Liver failure induces a systemic inflammatory response. Prevention by recombinant N-terminal bactericidal/permeability-increasing protein, Am J Pathol, 147, 1428–1440, 1995

    PubMed  CAS  Google Scholar 

  • Carlos T.M. and Harlan J.M., Leukocyte-endothelial adhesion molecules, Blood, 84, 2068–2101, 1994

    PubMed  CAS  Google Scholar 

  • Erzurum S.C., Downey G.P., Doherty D.E., Schwab B. III, Elson E.L., Worthen G.S., Mechanisms of lipopolysaccharide-induced neutrophil retention, Relative contributions of adhesive and cellular mechanical properties, J Immunol, 149, 154–162, 1992

    PubMed  CAS  Google Scholar 

  • Essani N.A., Fisher M.A., Farhood A., Manning A.M., Smith C.W., Jaeschke H., Cytokine-induced upregulation of hepatic intercellular adhesion molecule-1 messenger RNA expression and its role in the pathophysiology of murine endotoxin shock and acute liver failure, Hepatology, 21, 1632–1639, 1995a

    PubMed  CAS  Google Scholar 

  • Essani N., Mcguire G.M., Manning A.M., Jaeschke H., Differential induction of mRNA for ICAM-1 and selectins in hepatocytes, Kupffer cells and endothelial cells during endotoxemia, Biochem Biophys Res Comm, 211, 74–82, 1995b

    CAS  Google Scholar 

  • Evangelista V., Manarini S., Rotondo S., Martelli N., Polischuk R., Mcgregor J.L., Degaetano G., Cerletti C., Platelet/polymorphonuclear leukocyte interaction in dynamic conditions: evidence of adhesion cascade and cross talk between P-selectin and beta 2 integrin CDllb/CD18, Blood, 88,4183–4194, 1996

    PubMed  CAS  Google Scholar 

  • Farhood A., Mcguire G.M., Manning A.M., Miyasaka M., Smith C.W., Jaeschke H., Intercellular adhesion molecule 1 (ICAM-1) expression and its role in neutrophil-induced ischemia-reperfusion injury in rat liver, J Leukoc Biol, 57, 368–374, 1995

    PubMed  CAS  Google Scholar 

  • Fisher C.J. JR and Zheng Y., Potential strategies for inflammatory mediator manipulation: retrospect and prospect, World J Surg, 20, 447–453, 1996

    Article  PubMed  Google Scholar 

  • Granger D.N. and Kubes P., The microcirculation and inflammation: modulation of leukocyteendothelial cell adhesion, J Leukoc Biol, 55, 662–675, 1994

    PubMed  CAS  Google Scholar 

  • Ho J.S., Buchweitz J.P., Roth R.A., Ganey P.E., Identification of factors from rat neutrophils responsible for cytotoxicity to isolated hepatocytes, J Leukoc Biol, 59, 716–724, 1996

    PubMed  CAS  Google Scholar 

  • Issekutz A.C. and Lopes N., Endotoxin activation of endothelium for polymorphonuclear leukocyte transendothelial migration and modulation by interferon-y, Immunology, 79, 600–607, 1993

    PubMed  CAS  Google Scholar 

  • Kirkpatrick C.J., Bittinger F., Klein C.L., Hauptmann S., Klosterhalfen B., The role of the microcirculation in multiple organ dysfunetion Syndrome (MODS): a review and perspective, Virchows Arch, 427, 461–476, 1996

    Article  PubMed  CAS  Google Scholar 

  • Lamy M. and Deby-Dupont G., Is sepsis a mediator-inhibitor mismatch?, Intensive Care Med, 21, S250–S257, 1995

    Article  PubMed  Google Scholar 

  • Lawrence M.B. and Springer T.A., Leukocytes roll on a selectin at physiologic flow rates: Distinction from and prerequisite for adhesion through integrins, Cell, 65, 859–873, 1991

    Article  PubMed  CAS  Google Scholar 

  • Menger M.D. and Vollmar B., Adhesion molecules as determinants of disease: From molecular biology to surgical research, Br J Surg 83, 588–601, 1996

    Article  PubMed  CAS  Google Scholar 

  • Menger M.D., Vollmar B., Glasz J., Müller M.J., Post S., Messmer K., Hepatic ischemia/reperfusion, Prog Appl Microcirc, 19,106–124, 1993

    Google Scholar 

  • Morigi M., Micheletti G., Figliuzzi M., Imberti B., Karmali M.A., Remuzzi A., Remuzzi G., Zoja C., Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions, Blood, 86,4553–4558, 1995a

    PubMed  CAS  Google Scholar 

  • Morigi M., Zoja C., Figliuzzi M., Foppolo M., Micheletti G., Bontempelli M., Saronni M., Remuzzi G., Remuzzi A., Fluid shear stress modulates surface expression of adhesion molecules by endothelial cells, Blood, 85, 1696–1703, 1995b

    PubMed  CAS  Google Scholar 

  • Moser R., Schleiffenbaum B., Groscurth P., Fehr J., Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage, J Clin Invest, 83, 444–455, 1989

    Article  PubMed  CAS  Google Scholar 

  • Muller W.A., Weigl S.A., Deng X., Phillips D.M., PECAM-1 is required for transendothelial migration of leukocytes, J Exp Med, 178, 449–460, 1993

    Article  PubMed  CAS  Google Scholar 

  • Nieuwenhuijzen G.A.P., Deitche . A., Goris R.J.A., Infection, the gut and the development of the multiple organ dysfimction sydrome, Eir J Surg, 162, 259–273, 1996

    CAS  Google Scholar 

  • Nunes F.A., Kumar C., Chance B., Brass C., Chemiluminescent measurement of increased free radical formation after ischemia/reperfusion, Dig Dis Sei, 40, 1045–1053, 1995

    Article  CAS  Google Scholar 

  • Partrick D.A., Moore F.A., Moore E.E., Barnett C.C. JR, Silliman C.C., Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure, New Horiz, 4, 194–210, 1996

    PubMed  CAS  Google Scholar 

  • Pastores S.M., Katz D.P., Kvetan V., splanchnic ischemia and gut mucosal injury in sepsis and the multiple organ dysfimction Syndrome, Am J Gastroenterol, 91, 1697–1710, 1996a

    PubMed  CAS  Google Scholar 

  • Pastores S.M., Thakkar A., Gennis P., Katz . P, Kvetan V., Posttraumatic multiple-organ dysfunetion Syndrome: role of mediators in systemic inflammation and subsequent organ failure, Acad Emerg Med, 3, 611–622, 1996b

    Article  PubMed  CAS  Google Scholar 

  • Regel G., Grotz M., Weltner T., Sturm J.A., Tscherne H., Pattem of organ failure following severe trauma, World J Surg, 20, 422–429, 1996

    Article  PubMed  CAS  Google Scholar 

  • Rossaint R., Extracorporal membrane oxy genation for transport of hypoxaemic patients with severe ARDS, Br J Anaesth, 78, 241–246, 1997

    PubMed  CAS  Google Scholar 

  • Rücker M., Finckh B., Kohlschütter A., Menger M.D., Vollmar B., Dietary vitamin E does not protect from endotoxin-induced hepatic microvascular dysfimction, Cell Mol Life Sei, 53, 294–302, 1997

    Article  Google Scholar 

  • Rüttinger D., Vollmar B., Wanner G.A., Messmer K., In vivo assessment of hepatic alterations following gadolinium chloride-induced Kupffer cell blockade, J Hepatol, 25, 960–967, 1996

    Article  PubMed  Google Scholar 

  • Samarasinghe D.A. and Farrell G.C., The central role of sinusoidal endothelial cells in hepatic hypoxia-reoxygenation injury in the rat, Hepatology, 24, 1230–1237, 1996

    Article  PubMed  CAS  Google Scholar 

  • Sauaia A., Moore F.A., Moore E.E., Lezotte D.C., Early risk factors for postinjury multiple organ failure, World J Surg, 20, 392–400, 1996

    Article  PubMed  CAS  Google Scholar 

  • Smedley L.A., Tonnesen M.G., Sandhaus R.A, Haslett C., Guthrie L . A, Johnston R.B. JR, Henson P.M., Worthen G.S., Neutrophil-mediated injury to endothelial cells. Enhancement by endotoxin and essential role of neutrophil elastase, J Clin Invest, 77, 1233–1243,1986

    Article  Google Scholar 

  • Vissers M.C.M, George P.M., Bathurst I.C, Brennan S.O., Winterbourn C.C., Cleavage and inactivation of arantitrypsin by metalloproteinases released from neutrophils, J Clin Invest, 82, 706– 711,1988

    Article  PubMed  CAS  Google Scholar 

  • Vollmar B. and Menger M . D., Assessment of microvascular oxygen supply and tissue oxygenation in hepatic ischemia/reperfusion, Adv Exp Med Biol, 1997

    Google Scholar 

  • Vollmar B., Glasz J., Leiderer R., Post S., Menger M.D., Hepatic microcirculatory perfusion failure is a determinant for liver dysfunetion in warm ischemia-reperfusion, Am J Pathol, 145, 1421–1431, 1994a

    PubMed  CAS  Google Scholar 

  • Vollmar B., Glasz J., Post S., Menger M.D., Depressed phagocytic activity of Kupffer cells after warm ischemia-reperfusion of the liver, J Hepatol, 20, 301–304, 1994b

    Article  PubMed  CAS  Google Scholar 

  • Vollmar B., Lang G., Menger M.D., Messmer K., Hypertonie hydroxyethylstarch restores hepatic microvascular perfusion in hemorrhagic shock, Am J Physiol, 266, H1927–H1934, 1994c

    PubMed  CAS  Google Scholar 

  • Vollmar B., Menger M.D., Glasz J., Leiderer R., Messmer K., Impact of leukocyte-endothelial cell interaction in hepatic ischemia-reperfusion injury, Am J Physiol, 267, G786–G793, 1994d

    PubMed  CAS  Google Scholar 

  • Vollmar B., Glasz J., Menger M.D., Messmer K., Leukocytes contribute to hepatic ischemiareperfusion injury via ICAM-1 mediated microvascular adherence, Surgery, 117, 195–200, 1995a

    Article  PubMed  CAS  Google Scholar 

  • Vollmar B., Senkel A., Menger M.D., In vivo evidence that intercellular adhesion molecule-1 (ICAM-1) does not mediate endotoxin-induced hepatic leukocyte-endothelial cell interaction, J Hepatol, 23, 613–616, 1995b

    Article  CAS  Google Scholar 

  • Vollmar B., Glasz J., Post S., Menger M . D., Role of microcirculatory derangements in manifestation of portal triad cross-clamping-induced hepatic reperfusion injury, J Surg Res, 60,49–54, 1996a

    Article  PubMed  CAS  Google Scholar 

  • Vollmar B., Richter S., Menger M . D., Leukocyte stasis in hepatic sinusoids, Am J Physiol, 270, G798–G803, 1996b

    PubMed  CAS  Google Scholar 

  • Vollmar B, Rücker M., Menger M.D., A new method for the intravital microscopic quantification of hepatic sinusoidal perfusion failure using the dye Bis-benzamide H33342, Microvasc Res, 51, 250– 259,1996c

    Article  PubMed  CAS  Google Scholar 

  • Vollmar B., Rüttinger D., Wanner G . A., Leiderer R., Menger M . D., Modulation of Kupffer cell activity by gadolinium chloride in endotoxemic rats, Shock, 6, 434–441, 1996d

    Article  PubMed  CAS  Google Scholar 

  • Vollmar B., Burkhardt M., Minor T., Klauke H., Menger M.D., High resolution microscopic determination of hepatic NADH fluorescence for in vivo monitoring of tissue oxygenation during hemorrhagic shock and resuscitation, Microvasc Res, 1997a

    Google Scholar 

  • Vollmar B., Richter S., Menger M.D., Liver ischemia/reperfusion induces an increase of microvascular leukocyte flux, but not heterogeneity of leukocyte trafficking, Liver, 17, 93–98, 1997b

    PubMed  CAS  Google Scholar 

  • Vollmar B., Rüttinger D., Menger M.D., Monitoring of microvascular hemoglobin oxygenation in liver and skeletal muscle tissue of endotoxin-exposed rats using reflection spectrophotometry, Adv Exp Med Biol, 1997c

    Google Scholar 

  • Vollmar B., Wolf B., Siegmund S., Katsen A.D., Menger M.D., Lymph vessel expansion and funetion in the development of hepatic fibrosis and cirrhosis, Am J Pathol, 1997d

    Google Scholar 

  • Waydhas C., Nast-Kolb D., Trupka A., Zettl R., Kick M., Wiesholler J., Schweiberer L., Jochum M., Posttraumatic inflammatory response, secondary Operations, and late multiple organ failure, J Trauma, 40, 624–631, 1996

    Article  PubMed  CAS  Google Scholar 

  • Weiss S.J., Tissue destruetion by neutrophils, N Engl J Med, 320, 365–376, 1989

    Article  PubMed  CAS  Google Scholar 

  • Welbourn C.R.B., Goldman G., Paterson I.S., Valeri C.R., Shepro D., Hechtman H.B., Pathophysiology of ischaemia-reperfusion injury: Central role of the neutrophil, Br J Surg. 78. 651– 655 1991

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi Y., Akizuki E., Ichiguchi O., Matsumura F., Goto M., Miyanari N., Mori K., Yamada S., Ogawa M., Neutrophil elastase inhibitor reduces neutrophil chemoattractant production after ischemia-reperfusion in rat liver, Gastroenterology, 112, 551–560, 1997

    Article  PubMed  CAS  Google Scholar 

  • Zhang J.X., Jones D.V., Clemens M.G., Effect of activation on neutrophil-induced hepatic microvascular injury in isolated rat liver, Shock, 1, 273–278, 1994

    Article  PubMed  CAS  Google Scholar 

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Vollmar, B. (2000). Bedeutung der Leukozyten-Endothelzell- Interaktion für die Manifestation der Leberfunktionsstörung nach Ischämie/Reperfusion und Endotoxinämie. In: Schöffl, H., et al. Forschung ohne Tierversuche 2000. Ersatz- und Ergänzungsmethoden zu Tierversuchen. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6760-1_43

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  • DOI: https://doi.org/10.1007/978-3-7091-6760-1_43

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