Platelet activation by CD9 monoclonal antibodies is mediated by the Fc gamma II receptor.
The function of the human cell surface CD9 antigen is not known, yet monoclonal antibodies (mAbs) of the IgG1 subclass in the CD9 cluster induce activation of platelets. Previously it had been shown that this activation pathway is comparable both in kinetics and extent to physiological agonists such as thrombin. Here it is demonstrated that activation with CD9 mAbs depends on interaction of the Fc part of the CD9 antibody molecule with Fc receptors on the platelet surface, since: (i) mAb directed against the Fc receptor totally blocked the platelet response to CD9 mAb; and (ii) F(ab')2 fragments of the CD9 mAb SYB-1 which bound to platelets, as demonstrated by flow cytometry, failed to activate them. Furthermore, platelet activation by CD9 mAb closely paralleled the activation caused by cross-linking Fc receptors when comparing: (i) kinetics and extent of aggregation; (ii) thromboxane synthesis; (iii) calcium flux; and (iv) the cytoplasmic alkalinization response. Thus it is concluded that CD9 antigen itself does not necessarily participate in stimulus-response coupling leading to platelet activation by CD9 mAbs, and that this activation can be entirely accounted for by the Fc receptor pathway mechanism. The results suggest a possible novel mechanism for platelet consumption in cases of immune thrombocytopenia.
Worthington
R E
RE
Department of Medical Biology, University of Tennessee Medical Center, Knoxville.
Carroll
R C
RC
Boucheix
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins; D015539:Platelet Activation / Q000276:immunology*; D010974:Platelet Aggregation / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology* / Q000502:physiology; D060245:Tetraspanin 29; D013929:Thromboxane B2 / Q000097:blood
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D060245:Tetraspanin 29; D013929:Thromboxane B2; D002118:Calcium