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

• Published in: The American journal of pathology Vol. 144; no. 3; pp. 592 - 598
• Main Authors: Seekamp, A, Till, GO, Mulligan, MS, Paulson, JC, Anderson, DC, Miyasaka, M, Ward, PA
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01-03-1994; American Society for Investigative Pathology
• Subjects: Animals; Antibodies - immunology; Antibodies - pharmacology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Adhesion Molecules - analysis; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - physiology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; E-Selectin; L-Selectin; Lung - chemistry; Lung - pathology; Lung - physiology; Male; Medical sciences; 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; Focal lesion; Animal model; Pathophysiology; Lung; Cell adhesion molecule; Cardiovascular disease; Experimental study; Striated muscle; Prevention; Vascular disease; Arteriopathy; Reperfusion; Ischemia; Animal
• ISSN: 0002-9440; 1525-2191

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.