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characterize the activation of platelet integrin αⅡbβ3 induced by two anti human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4, and investigate their potential mechanism of action Methods Using 125 I labeled human fibrinogen (Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured Results HI117 and SJ9A4 (10?μg/ml and 20?μg/ml) induced specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin αⅡbβ3 Further study indicated that HI117 and SJ9A4 induced integrin αⅡbβ3 activation independent of platelet Fc receptors, and that HI117 and SJ9A4 induced integrin αⅡbβ3 activation was inhibited by pretreatment of platelets with sphingosine, aspirin, apyrase, and/or PGI 2 Conclusions Anti platelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin αⅡbβ3 activation independent of Fc receptors Three signaling pathways, namely thromboxane, secreted ADP, and cAMP pathways, may be involved in the process, with protein kinase C activation presumably being the common step of the three pathways
characterize the activation of platelet integrin αⅡbβ3 induced by two anti human platelet tetraspanin monoclonal antibodies (mAbs), HI 117 and SJ9A4, and investigate their potential mechanism of action Methods Using 125 I labeled human fibrinogen (Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured Results HI F7 and SJ9A4 (10 μg / ml and 20 μg / ml) induced specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin αⅡbβ3 Further study indicated that HI117 and SJ9A4 induced integrin αIIbβ3 activation independent of platelet Fc receptors, and that HI117 and SJ9A4 induced integrin αⅡbβ3 activation was inhibited by pretreatment of platelets with sphingosine, aspirin, apyrase, and / or PGI 2 Conclusions Antiplatelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin αⅡbβ3 activation independent of Fc receptors Three signaling pathway s, namely thromboxane, secreted ADP, and cAMP pathways, may be involved in the process, with protein kinase C activation presumably being the common step of the three pathways