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(Journal of Leukocyte Biology. 2002;72:262-270.)
© 2002 by Society for Leukocyte Biology

Concanavalin-A-induced liver injury is severely impaired in mice deficient in P-selectin

Anna Massaguer*,{dagger}, Sofía Perez-del-Pulgar{dagger},{ddagger}, Pablo Engel*,{dagger}, Joan Serratosa{dagger},§, Jaime Bosch{dagger},{ddagger} and Pilar Pizcueta{dagger},{ddagger}

{ddagger} Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Barcelona, Spain;
* Immunology Unit, Department of Cellular Biology and Pathology, Medical School, University of Barcelona, Spain;
§ Consejo Superior de Investigaciones Científicas, Barcelona, Spain; and
{dagger} Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain

Correspondence: Dr. Pilar Pizcueta, Fundació Clínic per a la Recerca Biomèdica, C/Villarroel 170, 08036 Barcelona, Spain. E-mail: pizcueta{at}medicina.ub.es

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.

Key Words: hepatitis • necrosis • T lymphocyte • adhesion molecule




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