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J Clin Invest. Jan 1995; 95(1): 134–141.
PMCID: PMC295389

Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein.

Abstract

The liver is highly susceptible to a number of pathological insults, including ischemia/reperfusion injury. One of the striking consequences of liver injury is the associated pulmonary dysfunction that may be related to the release of hepatic-derived cytokines. We have previously employed an animal model of hepatic ischemia/reperfusion injury, and demonstrated that this injury causes the production and release of hepatic-derived TNF, which mediates a neutrophil-dependent pulmonary microvascular injury. In this study, we have extended these previous observations to assess whether an interrelationship between TNF and the neutrophil chemoattractant/activating factor, epithelial neutrophil activating protein-78 (ENA-78), exists that may be accountable for the pathology of lung injury found in this model. In the context of hepatic ischemia/reperfusion injury, we demonstrated the following alterations in lung pathophysiology: (a) an increase in pulmonary microvascular permeability, lung neutrophil sequestration, and production of pulmonary-derived ENA-78; (b) passive immunization with neutralizing TNF antiserum resulted in a significant suppression of pulmonary-derived ENA-78; and (c) passive immunization with neutralizing ENA-78 antiserum resulted in a significant attenuation of pulmonary neutrophil sequestration and microvascular permeability similar to our previous studies with anti-TNF. These findings support the notion that pulmonary ENA-78 produced in response to hepatic-derived TNF is an important mediator of lung injury.

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  • Faist E, Baue AE, Dittmer H, Heberer G. Multiple organ failure in polytrauma patients. J Trauma. 1983 Sep;23(9):775–787. [PubMed]
  • Colletti LM, Remick DG, Burtch GD, Kunkel SL, Strieter RM, Campbell DA., Jr Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. J Clin Invest. 1990 Jun;85(6):1936–1943. [PMC free article] [PubMed]
  • Colletti LM, Burtch GD, Remick DG, Kunkel SL, Strieter RM, Guice KS, Oldham KT, Campbell DA., Jr The production of tumor necrosis factor alpha and the development of a pulmonary capillary injury following hepatic ischemia/reperfusion. Transplantation. 1990 Feb;49(2):268–272. [PubMed]
  • Sauder DN, Mounessa NL, Katz SI, Dinarello CA, Gallin JI. Chemotactic cytokines: the role of leukocytic pyrogen and epidermal cell thymocyte-activating factor in neutrophil chemotaxis. J Immunol. 1984 Feb;132(2):828–832. [PubMed]
  • Strieter RM, Lynch JP, 3rd, Basha MA, Standiford TJ, Kasahara K, Kunkel SL. Host responses in mediating sepsis and adult respiratory distress syndrome. Semin Respir Infect. 1990 Sep;5(3):233–247. [PubMed]
  • Yoshimura T, Matsushima K, Oppenheim JJ, Leonard EJ. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1). J Immunol. 1987 Aug 1;139(3):788–793. [PubMed]
  • Strieter RM, Lukacs NW, Standiford TJ, Kunkel SL. Cytokines. 2. Cytokines and lung inflammation: mechanisms of neutrophil recruitment to the lung. Thorax. 1993 Jul;48(7):765–769. [PMC free article] [PubMed]
  • Walz A, Burgener R, Car B, Baggiolini M, Kunkel SL, Strieter RM. Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin 8. J Exp Med. 1991 Dec 1;174(6):1355–1362. [PMC free article] [PubMed]
  • Baggiolini M, Walz A, Kunkel SL. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. [PMC free article] [PubMed]
  • Matsushima K, Oppenheim JJ. Interleukin 8 and MCAF: novel inflammatory cytokines inducible by IL 1 and TNF. Cytokine. 1989 Nov;1(1):2–13. [PubMed]
  • Richmond A, Balentien E, Thomas HG, Flaggs G, Barton DE, Spiess J, Bordoni R, Francke U, Derynck R. Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin. EMBO J. 1988 Jul;7(7):2025–2033. [PMC free article] [PubMed]
  • Strieter RM, Kunkel SL, Burdick MD, Lincoln PM, Walz A. The detection of a novel neutrophil-activating peptide (ENA-78) using a sensitive ELISA. Immunol Invest. 1992 Oct;21(6):589–596. [PubMed]
  • Hayashi H, Chaudry IH, Clemens MG, Baue AE. Hepatic ischemia models for determining the effects of ATP-MgCl2 treatment. J Surg Res. 1986 Feb;40(2):167–175. [PubMed]
  • Obayashi T. Addition of perchloric acid to blood samples for colorimetric limulus test using chromogenic substrate: comparison with conventional procedures and clinical applications. J Lab Clin Med. 1984 Sep;104(3):321–330. [PubMed]
  • Nguyen DT, Eskandai MK, DeForge LE, Raiford CL, Strieter RM, Kunkel SL, Remick DG. Cyclosporin a modulation of tumor necrosis factor gene expression and effects in vitro and in vivo. J Immunol. 1990 May 15;144(10):3822–3828. [PubMed]
  • Strieter RM, Chensue SW, Basha MA, Standiford TJ, Lynch JP, Baggiolini M, Kunkel SL. Human alveolar macrophage gene expression of interleukin-8 by tumor necrosis factor-alpha, lipopolysaccharide, and interleukin-1 beta. Am J Respir Cell Mol Biol. 1990 Apr;2(4):321–326. [PubMed]
  • Lukacs NW, Kunkel SL, Strieter RM, Warmington K, Chensue SW. The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg-induced granulomatous inflammation. J Exp Med. 1993 Jun 1;177(6):1551–1559. [PMC free article] [PubMed]
  • Green TP, Johnson DE, Marchessault RP, Gatto CW. Transvascular flux and tissue accrual of Evans blue: effects of endotoxin and histamine. J Lab Clin Med. 1988 Feb;111(2):173–183. [PubMed]
  • Linderkamp O, Mader T, Butenandt O, Riegel KP. Plasma volume estimation in severely ill infants and children using a simplified Evans blue method. Eur J Pediatr. 1977 Jun 1;125(2):135–141. [PubMed]
  • Saria A, Lundberg JM. Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues. J Neurosci Methods. 1983 May;8(1):41–49. [PubMed]
  • Goldblum SE, Wu KM, Jay M. Lung myeloperoxidase as a measure of pulmonary leukostasis in rabbits. J Appl Physiol (1985) 1985 Dec;59(6):1978–1985. [PubMed]
  • Till GO, Morganroth ML, Kunkel R, Ward PA. Activation of C5 by cobra venom factor is required in neutrophil-mediated lung injury in the rat. Am J Pathol. 1987 Oct;129(1):44–53. [PMC free article] [PubMed]
  • Chensue SW, Remick DG, Shmyr-Forsch C, Beals TF, Kunkel SL. Immunohistochemical demonstration of cytoplasmic and membrane-associated tumor necrosis factor in murine macrophages. Am J Pathol. 1988 Dec;133(3):564–572. [PMC free article] [PubMed]
  • Schlag G, Redl H, Hallström S. The cell in shock: the origin of multiple organ failure. Resuscitation. 1991 Apr;21(2-3):137–180. [PubMed]
  • Mandell GL. ARDS, neutrophils, and pentoxifylline. Am Rev Respir Dis. 1988 Nov;138(5):1103–1105. [PubMed]
  • Flick MR, Perel A, Staub NC. Leukocytes are required for increased lung microvascular permeability after microembolization in sheep. Circ Res. 1981 Mar;48(3):344–351. [PubMed]
  • Baird BR, Cheronis JC, Sandhaus RA, Berger EM, White CW, Repine JE. O2 metabolites and neutrophil elastase synergistically cause edematous injury in isolated rat lungs. J Appl Physiol (1985) 1986 Dec;61(6):2224–2229. [PubMed]
  • Weiss SJ, Regiani S. Neutrophils degrade subendothelial matrices in the presence of alpha-1-proteinase inhibitor. Cooperative use of lysosomal proteinases and oxygen metabolites. J Clin Invest. 1984 May;73(5):1297–1303. [PMC free article] [PubMed]
  • Arnaout MA. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood. 1990 Mar 1;75(5):1037–1050. [PubMed]
  • Springer TA. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. [PubMed]

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