The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1.
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 beta2-integrin Mac-1 (alphaMbeta2, 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 beta2-integrin Mac-1 and to a lower extent with p150.95 (alphaXbeta2, CD11c/CD18) but not with LFA-1 (alphaLbeta2, CD11a/CD18) or with beta1-integrins. These results were corroborated by analysis of K562 erythroleukemic cells transfected with different heterodimeric beta2-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.
Santoso
Sentot
S
Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University, D-35385 Giessen, Germany. sentot.santoso@immunologie.med.uni-giessen.de
Sachs
Ulrich J H
UJ
Kroll
Hartmut
H
Linder
Monica
M
Ruf
Andreas
A
Preissner
Klaus T
KT
Chavakis
Triantafyllos
T
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001792:Blood Platelets / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000235:genetics / Q000276:immunology; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D062726:Junctional Adhesion Molecules; D020014:K562 Cells; D007962:Leukocytes / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D062726:Junctional Adhesion Molecules; D016177:Macrophage-1 Antigen