UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin alphaIIbbeta3.
UV-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/m(2)) caused platelet aggregation, which was dependent on integrin alphaIIbbeta3 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 alphaIIbbeta3 in Chinese hamster ovary (CHO) cells, an environment in which physiologic agonists fail to activate. Activation of alphaIIbbeta3 requires talin binding to the beta3 tail, yet alphaIIbbeta3-Delta724 (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 beta(1) and beta(2) 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 alphaIIbbeta3. Thus, UV-C appears to activate alphaIIbbeta3 not by affecting intracellular signal transduction, but by reduction of disulfide bonds regulating integrin conformation.
Verhaar
Robin
R
Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands.
Dekkers
David W C
DW
De Cuyper
Iris M
IM
Ginsberg
Mark H
MH
de Korte
Dirk
D
Verhoeven
Arthur J
AJ
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry*; D016466:CHO Cells; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004220:Disulfides / Q000528:radiation effects*; D006801:Humans; D009504:Neutrophils; D010782:Photolysis; D010974:Platelet Aggregation / Q000528:radiation effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism / Q000528:radiation effects*; D010980:Platelet Membrane Glycoproteins / Q000528:radiation effects; D011487:Protein Conformation; D014466:Ultraviolet Rays / Q000009:adverse effects*
D004220:Disulfides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins
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