Concanavalin-A-induced liver injury is severely impaired in mice deficient in P-selectin.
P-selectin (CD62P) is an adhesion molecule that mediates the initial attachment of leukocytes to activated platelets and endothelial cells in damaged tissues. We evaluated the role of P-selectin in concanavalin A (Con A)-induced hepatitis, a model characterized by CD4(+) T cell activation and infiltration of the liver. Con A injection induced transient P-selectin expression on hepatic venules and platelets. Mice lacking P-selectin showed impaired lymphocyte adhesion to liver venules and sinusoids, a striking reduction in intrasinusoidal occlusion, and decreased lymphocyte infiltration of liver parenchyma. The reduction in transaminase levels and the almost complete abolition of necrotic injury demonstrated that liver damage was lower in P-selectin-deficient mice. In wild-type mice, pretreatment with the P-selectin-blocking monoclonal antibody attenuated the sinusoidal occlusion and reduced the rise in transaminases after Con A treatment. These results implicate P-selectin in the development of Con A-induced liver injury and reveal the protective effect of blocking P-selectin in this hepatitis.
Massaguer
Anna
A
Immunology Unit, Department of Cellular Biology and Pathology, Medical School, University of Barcelona, Spain.
Perez-Del-Pulgar
Sofía
S
Engel
Pablo
P
Serratosa
Joan
J
Bosch
Jaime
J
Pizcueta
Pilar
P
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001327:Autoimmune Diseases / Q000628:therapy; D001792:Blood Platelets / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D002634:Chemotaxis, Leukocyte; D003208:Concanavalin A / Q000633:toxicity*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006487:Hemostasis; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis; D019007:P-Selectin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D003208:Concanavalin A; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase