Platelet activation by cross-linking HLA class I molecules and Fc receptor.
The effect on platelet activation of monoclonal antibodies directed against common determinants of the HLA class I heavy chain molecule was studied. Cross-linking W6/32, an anti-HLA class I of IgG2a subclass, led to platelet activation. Two other antibodies of the same subclass did not have this effect on platelets. The lack of activity of the F(ab')2 fragments suggests that the activation signal is mediated by the platelet Fc receptor (Fc gamma RII). Indeed, except for a higher sensitivity of W6/32 to aspirin and apyrase, activations by cross-linking IV-3 (an anti-Fc gamma RII) and W6/32 are similar at the level of InsP3 formation, calcium mobilization, pH modifications, and activation of protein kinase C and myosin kinase. When HLA class I molecules and Fc gamma RII are cross-linked together, platelet activation occurs. This is not observed when a control IgG2a is substituted for W6/32 or when CD9 and Fc receptor are cross-linked together. This suggests that HLA class I molecules and Fc gamma RII synergize to activate platelets.
Rubinstein
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E
Department of Medical Biology, University of Tennessee, Medical Center, Knoxville 37920.
Urso
I
I
Boucheix
C
C
Carroll
R C
RC
D000244:Adenosine Diphosphate / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001081:Apyrase / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D002118:Calcium / Q000097:blood; D003432:Cross-Linking Reagents; D003594:Cytoplasmic Granules / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000276:immunology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010750:Phosphoproteins / Q000097:blood; D015539:Platelet Activation / Q000276:immunology*; D010974:Platelet Aggregation / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D010750:Phosphoproteins; D011961:Receptors, Fc; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D015544:Inositol 1,4,5-Trisphosphate; D001081:Apyrase; D001241:Aspirin; D002118:Calcium