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. 1988 Mar;81(3):939–944. doi: 10.1172/JCI113407

A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits.

N B Vedder 1, R K Winn 1, C L Rice 1, E Y Chi 1, K E Arfors 1, J M Harlan 1
PMCID: PMC442549  PMID: 3278007

Abstract

Leukocytes have been shown to play an important role in the development of isolated organ injury after experimental ischemia and reperfusion. To examine the role of leukocytes in generalized ischemia-reperfusion injury we used the MAb 60.3 (directed to the human leukocyte adherence glycoprotein, CD18) to block leukocyte adherence functions in a rabbit model of hemorrhagic shock and resuscitation. In control animals subjected to 1 h of shock (mean blood pressure 45 torr and mean cardiac output 30% of baseline) followed by resuscitation, only 29% survived 5 d. All had gross and histologic evidence of injury to lungs, liver, and gastrointestinal mucosa. In contrast, 100% of the MAb 60.3-treated animals survived 5 d (P less than 0.01) and organ injury was absent or markedly attenuated. The control animals also had a persistent acidosis, lost more weight, and had evidence of continued gastrointestinal bleeding in contrast to MAb 60.3-treated animals. We conclude that increased leukocyte adhesiveness plays an important role in the development of multiple organ injury and death after generalized ischemia-reperfusion and that this injury may be significantly reduced by blocking leukocyte adherence functions with the MAb 60.3.

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Selected References

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  1. Arfors K. E., Lundberg C., Lindbom L., Lundberg K., Beatty P. G., Harlan J. M. A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood. 1987 Jan;69(1):338–340. [PubMed] [Google Scholar]
  2. Beatty P. G., Ledbetter J. A., Martin P. J., Price T. H., Hansen J. A. Definition of a common leukocyte cell-surface antigen (Lp95-150) associated with diverse cell-mediated immune functions. J Immunol. 1983 Dec;131(6):2913–2918. [PubMed] [Google Scholar]
  3. Engler R. L., Dahlgren M. D., Morris D. D., Peterson M. A., Schmid-Schönbein G. W. Role of leukocytes in response to acute myocardial ischemia and reflow in dogs. Am J Physiol. 1986 Aug;251(2 Pt 2):H314–H323. doi: 10.1152/ajpheart.1986.251.2.H314. [DOI] [PubMed] [Google Scholar]
  4. Engler R. Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia. Fed Proc. 1987 May 15;46(7):2407–2412. [PubMed] [Google Scholar]
  5. Faist E., Baue A. E., Dittmer H., Heberer G. Multiple organ failure in polytrauma patients. J Trauma. 1983 Sep;23(9):775–787. doi: 10.1097/00005373-198309000-00002. [DOI] [PubMed] [Google Scholar]
  6. Glauser F. L., Fairman R. P. The uncertain role of the neutrophil in increased permeability pulmonary edema. Chest. 1985 Oct;88(4):601–607. doi: 10.1378/chest.88.4.601. [DOI] [PubMed] [Google Scholar]
  7. Goris R. J., te Boekhorst T. P., Nuytinck J. K., Gimbrère J. S. Multiple-organ failure. Generalized autodestructive inflammation? Arch Surg. 1985 Oct;120(10):1109–1115. doi: 10.1001/archsurg.1985.01390340007001. [DOI] [PubMed] [Google Scholar]
  8. Grisham M. B., Hernandez L. A., Granger D. N. Xanthine oxidase and neutrophil infiltration in intestinal ischemia. Am J Physiol. 1986 Oct;251(4 Pt 1):G567–G574. doi: 10.1152/ajpgi.1986.251.4.G567. [DOI] [PubMed] [Google Scholar]
  9. Harlan J. M., Killen P. D., Senecal F. M., Schwartz B. R., Yee E. K., Taylor R. F., Beatty P. G., Price T. H., Ochs H. D. The role of neutrophil membrane glycoprotein GP-150 in neutrophil adherence to endothelium in vitro. Blood. 1985 Jul;66(1):167–178. [PubMed] [Google Scholar]
  10. Harlan J. M. Neutrophil-mediated vascular injury. Acta Med Scand Suppl. 1987;715:123–129. doi: 10.1111/j.0954-6820.1987.tb09912.x. [DOI] [PubMed] [Google Scholar]
  11. Hernandez L. A., Grisham M. B., Twohig B., Arfors K. E., Harlan J. M., Granger D. N. Role of neutrophils in ischemia-reperfusion-induced microvascular injury. Am J Physiol. 1987 Sep;253(3 Pt 2):H699–H703. doi: 10.1152/ajpheart.1987.253.3.H699. [DOI] [PubMed] [Google Scholar]
  12. Jacob H. S. Complement-mediated leucoembolization: a mechanism of tissue damage during extracorporeal perfusions, myocardial infarction and in shock--a review. Q J Med. 1983 Summer;52(207):289–296. [PubMed] [Google Scholar]
  13. McCord J. M. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med. 1985 Jan 17;312(3):159–163. doi: 10.1056/NEJM198501173120305. [DOI] [PubMed] [Google Scholar]
  14. Mullane K. M., Read N., Salmon J. A., Moncada S. Role of leukocytes in acute myocardial infarction in anesthetized dogs: relationship to myocardial salvage by anti-inflammatory drugs. J Pharmacol Exp Ther. 1984 Feb;228(2):510–522. [PubMed] [Google Scholar]
  15. Petrone W. F., English D. K., Wong K., McCord J. M. Free radicals and inflammation: superoxide-dependent activation of a neutrophil chemotactic factor in plasma. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1159–1163. doi: 10.1073/pnas.77.2.1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Price T. H., Beatty P. G., Corpuz S. R. In vivo inhibition of neutrophil function in the rabbit using monoclonal antibody to CD18. J Immunol. 1987 Dec 15;139(12):4174–4177. [PubMed] [Google Scholar]
  17. Romson J. L., Hook B. G., Kunkel S. L., Abrams G. D., Schork M. A., Lucchesi B. R. Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation. 1983 May;67(5):1016–1023. doi: 10.1161/01.cir.67.5.1016. [DOI] [PubMed] [Google Scholar]
  18. Schmid-Schönbein G. W. Capillary plugging by granulocytes and the no-reflow phenomenon in the microcirculation. Fed Proc. 1987 May 15;46(7):2397–2401. [PubMed] [Google Scholar]
  19. Wallis W. J., Hickstein D. D., Schwartz B. R., June C. H., Ochs H. D., Beatty P. G., Klebanoff S. J., Harlan J. M. Monoclonal antibody-defined functional epitopes on the adhesion-promoting glycoprotein complex (CDw18) of human neutrophils. Blood. 1986 Apr;67(4):1007–1013. [PubMed] [Google Scholar]
  20. Weisfeldt M. L. Reperfusion and reperfusion injury. Clin Res. 1987 Jan;35(1):13–20. [PubMed] [Google Scholar]

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