title: In vivo platelet-endothelial cell interactions in response to major histocompatibility complex alloantibody.
abstract: 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.
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. cmorrell@jhmi.edu
authors.forename: Craig N
authors.initials: CN
authors.lastname: Morrell
authors.forename: Kazunori
authors.initials: K
authors.lastname: Murata
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Swaim
authors.forename: Emily
authors.initials: E
authors.lastname: Mason
authors.forename: Tanika V
authors.initials: TV
authors.lastname: Martin
authors.forename: Laura E
authors.initials: LE
authors.lastname: Thompson
authors.forename: Mathew
authors.initials: M
authors.lastname: Ballard
authors.forename: Karen
authors.initials: K
authors.lastname: Fox-Talbot
authors.forename: Barbara
authors.initials: B
authors.lastname: Wasowska
authors.forename: William M
authors.initials: WM
authors.lastname: Baldwin
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology / Q000473:pathology*; D002450:Cell Communication / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D007518:Isoantibodies / Q000008:administration & dosage / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023421:Models, Animal; D015539:Platelet Activation / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D007518:Isoantibodies