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

Am J Pathol. 1994 Mar;144(3):592-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / physiology*
  • E-Selectin
  • L-Selectin
  • Lung / chemistry
  • Lung / pathology
  • Lung / physiology
  • Male
  • Muscles / chemistry
  • Muscles / pathology
  • Muscles / physiology
  • Oligosaccharides / pharmacology
  • P-Selectin
  • Platelet Membrane Glycoproteins / analysis
  • Platelet Membrane Glycoproteins / immunology
  • Platelet Membrane Glycoproteins / physiology*
  • Rats
  • Reperfusion Injury / etiology
  • Reperfusion Injury / physiopathology*
  • Reperfusion Injury / prevention & control

Substances

  • Antibodies
  • Cell Adhesion Molecules
  • E-Selectin
  • Oligosaccharides
  • P-Selectin
  • Platelet Membrane Glycoproteins
  • sialyl-Le(a) oligosaccharide
  • L-Selectin