Journal article
Intrinsic apoptosis circumvents the functional decline of circulating platelets but does not cause the storage lesion
I Pleines, M Lebois, P Gangatirkar, AE Au, RM Lane, KJ Henley, M Kauppi, J Corbin, P Cannon, J Bernardini, I Alwis, KE Jarman, S Ellis, D Metcalf, SP Jackson, SM Schoenwaelder, BT Kile, EC Josefsson
Blood | AMER SOC HEMATOLOGY | Published : 2018
Abstract
The circulating life span of blood platelets is regulated by the prosurvival protein BCL-XL. It restrains the activity of BAK and BAX, the essential prodeath mediators of intrinsic apoptosis. Disabling the platelet intrinsic apoptotic pathway in mice by deleting BAK and BAX results in a doubling of platelet life span and concomitant thrombocytosis. Apoptotic platelets expose phosphatidylserine (PS) via a mechanism that is distinct from that driven by classical agonists. Whether there is any role for apoptotic PS in platelet function in vivo, however, is unclear. Apoptosis has also been associated with the platelet storage lesion (PSL), the constellation of biochemical deteriorations that occ..
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Funding Acknowledgements
This work was supported by project grants (1023029) (S.M.S. and E.C.J.) and (1079250) (E.C.J.), a program grant (1113577), fellowships (1063008) (B.T.K.) and (10794100) (S.P.J.), and an Independent Research Institutes Infrastructure Support Scheme Grant (9000220) from the Australian National Health and Medical Research Council; a fellowship and a research grant from the German Research Foundation (PL707/1-1 and PL707/2-1) (I.P.); a fellowship from the Lorenzo and Pamela Galli Charitable Trust (E.C.J.); a Victorian State Government Operational Infrastructure Support Grant; and the Australia Cancer Research Fund.