Role of selectins in local and remote tissue injury following ischemia and reperfusion.
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.
Seekamp
A
A
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Till
G O
GO
Mulligan
M S
MS
Paulson
J C
JC
Anderson
D C
DC
Miyasaka
M
M
Ward
P A
PA
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D019040:E-Selectin; D019041:L-Selectin; D008168:Lung / Q000737:chemistry / Q000473:pathology / Q000502:physiology; D008297:Male; D009132:Muscles / Q000737:chemistry / Q000473:pathology / Q000502:physiology; D009844:Oligosaccharides / Q000494:pharmacology; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D051381:Rats; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control
D000906:Antibodies; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D009844:Oligosaccharides; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; C058981:sialyl-Le(a) oligosaccharide; D019041:L-Selectin