Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1994 Mar;144(3):592–598.

Role of selectins in local and remote tissue injury following ischemia and reperfusion.

A Seekamp 1, G O Till 1, M S Mulligan 1, J C Paulson 1, D C Anderson 1, M Miyasaka 1, P A Ward 1
PMCID: PMC1887093  PMID: 7510457

Abstract

Ischemia (4-hour) followed by reperfusion (4-hour) of rat hind limbs results in local injury as well as remote (lung) injury. It has recently been shown that injury in this model is neutrophil- and cytokine-dependent and requires the beta 2 integrin adhesion molecules CD11a/CD18 and CD11b/CD18. The role of selectins in events leading to injury (as determined by leakage of albumin and by hemorrhage) was assessed either through the use of blocking antibodies to L-, E- or P-selectins or by the use of oligosaccharides that are reactive with selectins. Lung injury was found to be L- and E-selectin-dependent. When the ischemia and reperfusion times were reduced, lung injury was also found to be P-selectin dependent. In the case of hind limb injury involving the crural muscle mass, injury was L-selectin-dependent but independent of requirements for P- and E-selectin. Injury in both organs was blocked by the infusion of sialylated Lewis pentasaccharide, whereas sialyl-N-acetyllactosamine pentasaccharide failed to protect against injury. In general, when selectin-blocking approaches were protective, there were parallel reductions in tissue content of myeloperoxidase. These data underscore the role of selectins in ischemia-reperfusion injury and suggest that selectin requirements may vary with the vascular bed under study.

Full text

PDF
592

Selected References

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

  1. Anderson D. C., Springer T. A. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175–194. doi: 10.1146/annurev.me.38.020187.001135. [DOI] [PubMed] [Google Scholar]
  2. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
  3. Engler R. L. Free radical and granulocyte-mediated injury during myocardial ischemia and reperfusion. Am J Cardiol. 1989 Mar 7;63(10):19E–23E. doi: 10.1016/0002-9149(89)90225-7. [DOI] [PubMed] [Google Scholar]
  4. Lowe J. B., Stoolman L. M., Nair R. P., Larsen R. D., Berhend T. L., Marks R. M. ELAM-1--dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA. Cell. 1990 Nov 2;63(3):475–484. doi: 10.1016/0092-8674(90)90444-j. [DOI] [PubMed] [Google Scholar]
  5. Mulligan M. S., Johnson K. J., Todd R. F., 3rd, Issekutz T. B., Miyasaka M., Tamatani T., Smith C. W., Anderson D. C., Ward P. A. Requirements for leukocyte adhesion molecules in nephrotoxic nephritis. J Clin Invest. 1993 Feb;91(2):577–587. doi: 10.1172/JCI116237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Mulligan M. S., Lowe J. B., Larsen R. D., Paulson J., Zheng Z. L., DeFrees S., Maemura K., Fukuda M., Ward P. A. Protective effects of sialylated oligosaccharides in immune complex-induced acute lung injury. J Exp Med. 1993 Aug 1;178(2):623–631. doi: 10.1084/jem.178.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Mulligan M. S., Polley M. J., Bayer R. J., Nunn M. F., Paulson J. C., Ward P. A. Neutrophil-dependent acute lung injury. Requirement for P-selectin (GMP-140). J Clin Invest. 1992 Oct;90(4):1600–1607. doi: 10.1172/JCI116029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Mulligan M. S., Vaporciyan A. A., Miyasaka M., Tamatani T., Ward P. A. Tumor necrosis factor alpha regulates in vivo intrapulmonary expression of ICAM-1. Am J Pathol. 1993 Jun;142(6):1739–1749. [PMC free article] [PubMed] [Google Scholar]
  9. Mulligan M. S., Varani J., Dame M. K., Lane C. L., Smith C. W., Anderson D. C., Ward P. A. Role of endothelial-leukocyte adhesion molecule 1 (ELAM-1) in neutrophil-mediated lung injury in rats. J Clin Invest. 1991 Oct;88(4):1396–1406. doi: 10.1172/JCI115446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mulligan M. S., Ward P. A. Immune complex-induced lung and dermal vascular injury. Differing requirements for tumor necrosis factor-alpha and IL-1. J Immunol. 1992 Jul 1;149(1):331–339. [PubMed] [Google Scholar]
  11. Phillips M. L., Nudelman E., Gaeta F. C., Perez M., Singhal A. K., Hakomori S., Paulson J. C. ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science. 1990 Nov 23;250(4984):1130–1132. doi: 10.1126/science.1701274. [DOI] [PubMed] [Google Scholar]
  12. Picker L. J., Warnock R. A., Burns A. R., Doerschuk C. M., Berg E. L., Butcher E. C. The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140. Cell. 1991 Sep 6;66(5):921–933. doi: 10.1016/0092-8674(91)90438-5. [DOI] [PubMed] [Google Scholar]
  13. Seekamp A., Mulligan M. S., Till G. O., Smith C. W., Miyasaka M., Tamatani T., Todd R. F., 3rd, Ward P. A. Role of beta 2 integrins and ICAM-1 in lung injury following ischemia-reperfusion of rat hind limbs. Am J Pathol. 1993 Aug;143(2):464–472. [PMC free article] [PubMed] [Google Scholar]
  14. Seekamp A., Mulligan M. S., Till G. O., Smith C. W., Miyasaka M., Tamatani T., Todd R. F., 3rd, Ward P. A. Role of beta 2 integrins and ICAM-1 in lung injury following ischemia-reperfusion of rat hind limbs. Am J Pathol. 1993 Aug;143(2):464–472. [PMC free article] [PubMed] [Google Scholar]
  15. Seekamp A., Mulligan M. S., Till G. O., Ward P. A. Requirements for neutrophil products and L-arginine in ischemia-reperfusion injury. Am J Pathol. 1993 Apr;142(4):1217–1226. [PMC free article] [PubMed] [Google Scholar]
  16. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  17. Tamatani T., Kuida K., Watanabe T., Koike S., Miyasaka M. Molecular mechanisms underlying lymphocyte recirculation. III. Characterization of the LECAM-1 (L-selectin)-dependent adhesion pathway in rats. J Immunol. 1993 Mar 1;150(5):1735–1745. [PubMed] [Google Scholar]
  18. Welbourn C. R., 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. 1991 Jun;78(6):651–655. doi: 10.1002/bjs.1800780607. [DOI] [PubMed] [Google Scholar]
  19. Weyrich A. S., Ma X. Y., Lefer D. J., Albertine K. H., Lefer A. M. In vivo neutralization of P-selectin protects feline heart and endothelium in myocardial ischemia and reperfusion injury. J Clin Invest. 1993 Jun;91(6):2620–2629. doi: 10.1172/JCI116501. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES