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(Circulation Research. 2008;102:777.)
© 2008 American Heart Association, Inc.

Integrative Physiology

In Vivo Platelet–Endothelial Cell Interactions in Response to Major Histocompatibility Complex Alloantibody

Craig N. Morrell, Kazunori Murata, Anne Marie Swaim, Emily Mason, Tanika V. Martin, Laura E. Thompson, Mathew Ballard, Karen Fox-Talbot, Barbara Wasowska, William M. Baldwin, III

From the Departments of Molecular and Comparative Pathobiology (C.N.M., A.M.S., E.M., T.V.M., L.E.T.) and Pathology (K.M., K.F.-T., B.W., W.M.B.) and Graduate Program in Immunology (M.B.), The Johns Hopkins University School of Medicine, Baltimore, Md.

Correspondence to Craig N. Morrell, The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 853, Baltimore, MD 21205. E-mail cmorrell{at}jhmi.edu

Platelets recruit leukocytes and mediate interactions between leukocytes and endothelial cells. Most studies examining this important platelet immune function have focused on the development of atherosclerosis, but similar mechanisms may contribute to acute and chronic vascular lesions in transplants. Platelets have been described as markers of transplant rejection, but little investigation has critically examined a role for platelets in transplant vasculopathy and, in particular, alloantibody-mediated transplant rejection. We now demonstrate using a skin transplant model that alloantibody indirectly induces platelet activation and rolling in vivo. Repeated IgG2a alloantibody injections result in sustained platelet–endothelial interactions and vascular pathology, including von Willebrand factor release, small platelet thrombi, and complement deposition. Maintenance of continued platelet–endothelial interactions are dependent on complement activation. Furthermore, we demonstrate that platelets recruit leukocytes to sites of alloantibody deposition and sustain leukocyte–endothelial cell interactions in vivo. Taken together, our model demonstrates an important role for platelets in alloantibody induced transplant rejection.

Key Words: platelet • transplant • alloantibody • endothelial • leukocyte