Skip to main content
PMC home page
Annals of Surgery logoLink to Annals of Surgery
. 1990 Feb;211(2):196–201. doi: 10.1097/00000658-199002000-00012

Ischemia activates neutrophils but inhibits their local and remote diapedesis.

G Goldman 1, R Welbourn 1, J M Klausner 1, I S Paterson 1, L Kobzik 1, C R Valeri 1, D Shepro 1, H B Hechtman 1
PMCID: PMC1357964  PMID: 2301997

Abstract

Hindlimb ischemia and reperfusion results in local limb and distant lung injury. This study tests whether the mechanism of injury is by ischemia mediated polymorphonuclear leukocyte (PMN) activation and diapedesis. Anesthetized rabbits were subjected to three hours of hindlimb ischemia (n = 8) or sham ischemia (n = 4). PMN derived solely from the reperfused ischemic limb and assayed flow cytometrically displayed an oxidative burst of 135 /- 8 fentamoles dichlorofluorescein (fmDCF)/cell compared to preischemc levels of 74 +/- 14 fmDCF/cell (p less than 0.05). Additional aliquots of isolated neutrophils were treated with phorbol myristate acetate (PMA) 10(-7) M. In contrast to a 162% increase in oxidative burst before ischemia, neutrophils at ten minutes of reperfusion had an enhanced response to PMA of 336% (p less than 0.05). Plasma collected from the ischemic hindlimb at ten minutes of reperfusion when introduced into an abraded skin chamber or intratracheally induced diapedesis in nonischemic animals. PMN accumulations in the skin chamber were 1636 +/- 258 PMN/mm3 after three hours (n = 8) compared to 63 +/- 18 PMN/mm3 induced by sham plasma (n = 4, p less than 0.05). Introduction of ischemic plasma intratracheally into a lobar bronchus (n = 4) induced PMN accumulations after three hours, measured by bronchoalveolar lavage fluid of 19 +/- 2 X 10(4) PMN/mm3 compared to 5 +/- 1 X 10(4) PMN/mm3 with sham plasma (n = 4, p less than 0.05). Diapedesis was completely prevented (0-3 PMN/mm3, p less than 0.05) by introducing ischemic plasma into skin chambers in animals whose hindlimbs had been made ischemic (n = 6) or into chambers located on skin regions that had been previously made ischemic (n = 6). Similarly after hindlimb ischemia, lavage of the lung with ischemic plasma yielded few PMN 0-3/mm3 (p less than 0.05). These data indicate that ischemia and reperfusion lead to generation of a circulating component in plasma that causes an oxidative burst in PMN and inhibits their diapedesis but promotes diapedesis when applied extravascularly to a naive animal.

Full text

PDF
198

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anner H., Kaufman R. P., Jr, Kobzik L., Valeri C. R., Shepro D., Hechtman H. B. Pulmonary hypertension and leukosequestration after lower torso ischemia. Ann Surg. 1987 Nov;206(5):642–648. doi: 10.1097/00000658-198711000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anner H., Kaufman R. P., Jr, Kobzik L., Valeri C. R., Shepro D., Hechtman H. B. Pulmonary leukosequestration induced by hind limb ischemia. Ann Surg. 1987 Aug;206(2):162–167. doi: 10.1097/00000658-198708000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Gimbrone M. A., Jr Inducible endothelial functions in inflammation and coagulation. Semin Thromb Hemost. 1987 Oct;13(4):425–433. doi: 10.1055/s-2007-1003519. [DOI] [PubMed] [Google Scholar]
  4. Center D. M., Soter N. A., Wasserman S. I., Austen K. F. Inhibition of neutrophil chemotaxis in association with experimental angioedema in patients with cold urticaria: a model of chemotactic deactivation in vivo. Clin Exp Immunol. 1979 Jan;35(1):112–118. [PMC free article] [PubMed] [Google Scholar]
  5. Engler R. L., Schmid-Schönbein G. W., Pavelec R. S. Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol. 1983 Apr;111(1):98–111. [PMC free article] [PubMed] [Google Scholar]
  6. Goldman D. W., Goetzl E. J. Selective transduction of human polymorphonuclear leukocyte functions by subsets of receptors for leukotriene B4. J Allergy Clin Immunol. 1984 Sep;74(3 Pt 2):373–377. doi: 10.1016/0091-6749(84)90133-7. [DOI] [PubMed] [Google Scholar]
  7. Hoover R. L., Karnovsky M. J., Austen K. F., Corey E. J., Lewis R. A. Leukotriene B4 action on endothelium mediates augmented neutrophil/endothelial adhesion. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2191–2193. doi: 10.1073/pnas.81.7.2191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kaufman R. P., Jr, Klausner J. M., Anner H., Feingold H., Kobzik L., Valeri C. R., Shepro D., Hechtman H. B. Inhibition of thromboxane (Tx) synthesis by free radical scavengers. J Trauma. 1988 Apr;28(4):458–464. doi: 10.1097/00005373-198804000-00007. [DOI] [PubMed] [Google Scholar]
  9. Klausner J. M., Paterson I. S., Goldman G., Kobzik L., Rodzen C., Lawrence R., Valeri C. R., Shepro D., Hechtman H. B. Postischemic renal injury is mediated by neutrophils and leukotrienes. Am J Physiol. 1989 May;256(5 Pt 2):F794–F802. doi: 10.1152/ajprenal.1989.256.5.F794. [DOI] [PubMed] [Google Scholar]
  10. Klausner J. M., Paterson I. S., Goldman G., Kobzik L., Valeri C. R., Shepro D., Hechtman H. B. Thromboxane A2 mediates increased pulmonary microvascular permeability following limb ischemia. Circ Res. 1989 Jun;64(6):1178–1189. doi: 10.1161/01.res.64.6.1178. [DOI] [PubMed] [Google Scholar]
  11. Klausner J. M., Paterson I. S., Kobzik L., Valeri C. R., Shepro D., Hechtman H. B. Oxygen free radicals mediate ischemia-induced lung injury. Surgery. 1989 Feb;105(2 Pt 1):192–199. [PubMed] [Google Scholar]
  12. Klausner J. M., Paterson I. S., Valeri C. R., Shepro D., Hechtman H. B. Limb ischemia-induced increase in permeability is mediated by leukocytes and leukotrienes. Ann Surg. 1988 Dec;208(6):755–760. doi: 10.1097/00000658-198812000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Otani A., Hugli T. E. Leukocyte chemotaxis: a new in vivo testing technique. Inflammation. 1977 Mar;2(1):67–82. doi: 10.1007/BF00920876. [DOI] [PubMed] [Google Scholar]
  14. Paterson I. S., Klausner J. M., Goldman G., Kobzik L., Welbourn R., Valeri C. R., Shepro D., Hechtman H. B. Thromboxane mediates the ischemia-induced neutrophil oxidative burst. Surgery. 1989 Aug;106(2):224–229. [PubMed] [Google Scholar]
  15. Schmid-Schoenbein G. W., Fung Y. C., Zweifach B. W. Vascular endothelium-leukocyte interaction; sticking shear force in venules. Circ Res. 1975 Jan;36(1):173–184. doi: 10.1161/01.res.36.1.173. [DOI] [PubMed] [Google Scholar]
  16. Simpson P. J., Todd R. F., 3rd, Fantone J. C., Mickelson J. K., Griffin J. D., Lucchesi B. R. Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest. 1988 Feb;81(2):624–629. doi: 10.1172/JCI113364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Smith C. W., Rothlein R., Hughes B. J., Mariscalco M. M., Rudloff H. E., Schmalstieg F. C., Anderson D. C. Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration. J Clin Invest. 1988 Nov;82(5):1746–1756. doi: 10.1172/JCI113788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Vedder N. B., Winn R. K., Rice C. L., Chi E. Y., Arfors K. E., Harlan J. M. A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits. J Clin Invest. 1988 Mar;81(3):939–944. doi: 10.1172/JCI113407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wheeler M. E., Luscinskas F. W., Bevilacqua M. P., Gimbrone M. A., Jr Cultured human endothelial cells stimulated with cytokines or endotoxin produce an inhibitor of leukocyte adhesion. J Clin Invest. 1988 Oct;82(4):1211–1218. doi: 10.1172/JCI113718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Winsor T., Haumschild D. J., Winsor D. W., Wang Y., Luong T. N. Clinical application of laser Doppler flowmetry for measurement of cutaneous circulation in health and disease. Angiology. 1987 Oct;38(10):727–736. doi: 10.1177/000331978703801001. [DOI] [PubMed] [Google Scholar]
  21. Zimmerman G. A., Wiseman G. A., Hill H. R. Human endothelial cells modulate granulocyte adherence and chemotaxis. J Immunol. 1985 Mar;134(3):1866–1874. [PubMed] [Google Scholar]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

RESOURCES