期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 132, 期 3, 页码 339-348出版社
WILEY
DOI: 10.1111/j.1365-2141.2005.05878.x
关键词
bacitracin; integrin; thiol isomerase; platelet
类别
The platelet-specific integrin alpha IIb beta 3 has endogenous thiol isomerase activity associated with the CXXC motifs within the beta subunit. Using a highly purified form of bacitracin, a thiol isomerase inhibitor, we now provide further evidence of the functional significance of this enzymatic activity in integrin activation. In addition, we demonstrate a role for multiple thiol isomerases in platelet function. This bacitracin prevented platelet aggregation to thrombin and collagen, and directly inhibited alpha IIb beta 3 activation, as detected by PAC-1 binding. In parallel, bacitracin inhibited the endogenous thiol isomerase activity of purified alpha IIb beta 3 with a 50% inhibitory concentration of 15(.)5 mu mol/l. In order to determine whether the effects of bacitracin are solely mediated by inhibition of integrin enzymatic activity, we examined integrin-independent indices of platelet activation. We found bacitracin inhibited both platelet secretion (CD62P and CD63) and thromboxane (TxA(2)) production, with complete inhibition at different concentrations. Thus, we demonstrated a role for multiple thiol isomerases in platelet function. Taken together, these studies support a role for the endogenous integrin thiol isomerase activity in activation of alpha IIb beta 3 and highlight the novel regulation of platelet function by other, as yet undefined thiol isomerases.
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