HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin IIb3

UV-C irradiation has been shown to be effective for pathogen reduction in plate-let concentrates, but preliminary work indicated that UV-C irradiation of platelets can induce platelet aggregation. In this study, the mechanism underlying this phe-nomenon was investigated. Irradiation of platelets with UV-C light (1500 J/m2) caused platelet aggregation, which was dependent on integrin IIb3 activation (GPIIb/IIIa). This activation occurred de-spite treatment with several signal trans-duction inhibitors known to block platelet activation. UV-C also induced activation of recombinant IIb3 in Chinese ham-ster ovary (CHO) cells, an environment in which physiologic agonists fail to acti-vate. Activation of IIb3 requires talin binding to the 3 tail, yet IIb3-724 (lacking the talin binding site) was acti-vated by UV-C irradiation, excluding a requirement for talin binding. The UV-C effect appears to be general in that 1 and 2 integrins are also activated by UV-C. To explain these findings, we investigated the possibility of UV-C–induced photoly-sis of disulfide bonds, in analogy with the activating effect of reducing agents on integrins. Indeed, UV-C induced a marked increase in free thiol groups in platelet surface proteins including IIb3. Thus, UV-C appears to activate IIb3 not by affecting intracellular signal transduc-tion, but by reduction of disulfide bonds regulating integrin conformation. (Blood. 2008;112:4935-4939