A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2.
Activated platelets express P-selectin and release leukocyte chemoattractants; however, they have not been known to express integrin ligands important in the stabilization of leukocyte interactions with the vasculature. We now demonstrate the presence of intercellular adhesion molecular-2 (ICAM-2) (CD102), and lack of expression of other beta 2-integrin ligands, ICAM-1 (CD54) and ICAM-3 (CD50), on the surface of resting and stimulated platelets. ICAM-2 isolated from platelets migrates as a band of 59,000 M(r) in reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Staining of bone marrow aspirates with anti-ICAM-2 mAb demonstrates strong reactivity to megakaryocytes. Using frozen thin sections and immunogold labeling, the antigen was shown to be present on the plasma membrane and surface-connected canalicular system of resting platelets. The average number of ICAM-2 molecules per platelet is 3,000 +/- 230 and does not change after activation. In adhesion assays, resting and stimulated platelets were capable of binding through ICAM-2 to purified leukocyte function-associated antigen-1. Activation of T lymphocytes with PMA stimulated binding to platelets that was Mg2+ dependent and could be specifically inhibited by mAbs to either ICAM-2 or leukocyte function-associated antigen-1. ICAM-2 is the only known beta 2-integrin ligand present on platelets, suggesting that it may play an important role in leukocyte-platelet interactions in inflammation and thrombosis.
Diacovo
T G
TG
Harvard Medical School, Division of Newborn Medicine, Boston, Massachusetts 02115.
deFougerolles
A R
AR
Bainton
D F
DF
Springer
T A
TA
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000097:blood* / Q000302:isolation & purification; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D016253:Microscopy, Immunoelectron; D008970:Molecular Weight; D015539:Platelet Activation; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D013755:Tetradecanoylphorbol Acetate