UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin αIIbβ3

Abstract

AbstractUV-C irradiation has been shown to be effective for pathogen reduction in platelet concentrates, but preliminary work indicated that UV-C irradiation of platelets can induce platelet aggregation. In this study, the mechanism underlying this phenomenon was investigated. Irradiation of platelets with UV-C light (1500 J/m2) caused platelet aggregation, which was dependent on integrin αIIbβ3 activation (GPIIb/IIIa). This activation occurred despite treatment with several signal transduction inhibitors known to block platelet activation. UV-C also induced activation of recombinant αIIbβ3 in Chinese hamster ovary (CHO) cells, an environment in which physiologic agonists fail to activate. Activation of αIIbβ3 requires talin binding to the β3 tail, yet αIIbβ3-Δ724 (lacking the talin binding site) was activated by UV-C irradiation, excluding a requirement for talin binding. The UV-C effect appears to be general in that β1 and β2 integrins are also activated by UV-C. To explain these findings, we investigated the possibility of UV-C–induced photolysis 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 αIIbβ3. Thus, UV-C appears to activate αIIbβ3 not by affecting intracellular signal transduction, but by reduction of disulfide bonds regulating integrin conformation.