Neutrophils contribute to hepatic ischemia-reperfusion injury by a CD18-independent mechanism.
Hepatic ischemia-reperfusion injury is reported to be modulated by neutrophils (PMNs). The adhesion and emigration of PMNs that precede tissue inflammation and necrosis in other organs are mediated, in part, by the leukocyte adhesion complex CD11/CD18. In this study, the role of PMN adhesion via CD11/CD18 in isolated liver ischemia-reperfusion injury was examined in rabbits using a blocking monoclonal antibody (mAb 60.3) specific for the CD18 receptor. Vinblastine-induced neutropenia provided significant protection, confirming participation of neutrophils in the pathogenesis of hepatic injury. Inhibition of PMN adherence with mAb 60.3 did not ameliorate injury, as measured by aminotransferase concentrations or a histologic scoring system for injury severity. Histologic sections were scored for pattern and extent of injury as well as neutrophil association with injury. These results suggest a CD18-independent mechanism of neutrophil adhesion in the evolution of isolated hepatic ischemia-reperfusion injury.
Langdale
L A
LA
Department of Surgery, University of Washington, Seattle.
Flaherty
L C
LC
Liggitt
H D
HD
Harlan
J M
JM
Rice
C L
CL
Winn
R K
RK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D008099:Liver / Q000098:blood supply*; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology*; D009503:Neutropenia / Q000139:chemically induced; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D000637:Transaminases / Q000032:analysis; D014747:Vinblastine
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D014747:Vinblastine; D000637:Transaminases