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Address correspondence to Sentot Santoso, Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University Giessen, Langhansstrasse 7, D-35385 Giessen, Germany. Phone: 49-641-99-41518; Fax: 49-641-99-41529. E-mail: sentot.santoso{at}immunologie.med.uni-giessen.de
The recently described junctional adhesion molecules (JAMs) in man and mice are involved in homotypic and heterotypic intercellular interactions. Here, a third member of this family, human JAM-3, was identified and described as a novel counterreceptor on platelets for the leukocyte ß2-integrin Mac-1 (
Mß2, CD11b/CD18). With the help of two monoclonal antibodies, Gi11 and Gi13, against a 43-kD surface glycoprotein on human platelets, a full-length cDNA encoding JAM-3 was identified. JAM-3 is a type I transmembrane glycoprotein containing two Ig-like domains. Although JAM-3 did not undergo homophilic interactions, myelo-monocytic cells adhered to immobilized JAM-3 or to JAM-3–transfected cells. This heterophilic interaction was specifically attributed to a direct interaction of JAM-3 with the ß2-integrin Mac-1 and to a lower extent with p150.95 (Xß2, CD11c/CD18) but not with LFA-1 (Lß2, CD11a/CD18) or with ß1-integrins. These results were corroborated by analysis of K562 erythroleukemic cells transfected with different heterodimeric ß2-integrins and by using purified proteins. Moreover, purified JAM-3 or antibodies against JAM-3 blocked the platelet-neutrophil interaction, indicating that platelet JAM-3 serves as a counterreceptor for Mac-1 mediating leukocyte–platelet interactions. JAM-3 thereby provides a novel molecular target for antagonizing interactions between vascular cells that promote inflammatory vascular pathologies such as in atherothrombosis.
Key Words: monoclonal antibody • adhesion molecule • integrins • neutrophils • athero- thrombosis
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