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Riboflavin and ultraviolet light treatment of platelets triggers p 38 MAPK signaling: inhibition significantly improves in vitro platelet quality after pathogen reduction treatment
Author(s) -
Schubert Peter,
Coupland Danielle,
Culibrk Brankica,
Goodrich Raymond P.,
Devine Dana V.
Publication year - 2013
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12173
Subject(s) - phosphorylation , platelet , mapk/erk pathway , kinase , in vitro , signal transduction , chemistry , ultraviolet light , microbiology and biotechnology , pharmacology , biochemistry , biology , immunology , photochemistry
Background Pathogen reduction technologies ( PRTs ) significantly reduce the risk of transmission of infectious agents in platelet (PLT) concentrates; however, in vitro studies reveal a negative impact on PLT quality after PRT treatment including effects on PLT aggregation, integrin αIIbβ 3 conformation, and actin dynamics. Clinically, the interval between transfusions is shortened. Study Design and Methods Seeking to understand the biochemical mechanisms underlying these observed effects, we analyzed signal transduction in PLT concentrates after riboflavin and ultraviolet light ( UV ; M irasol) treatment and subsequent storage focusing on the phosphorylation levels of selected protein kinases. Results Among identified candidates, p 38 MAPK increased fourfold in phosphorylation after PRT . Incubation of PLT concentrates with a p 38 MAPK ‐specific inhibitor before PRT significantly improved numerous PLT quality measures. Phosphorylation levels of the p 38 MAPK substrates AKT , VASP , and HSP27 also decreased with inhibitor treatment. Phospho‐ HSP 27 decrease in the presence of the inhibitor correlated with a reduction in PLT activation determined by surface expression of P ‐selectin. Conclusion These findings support a model of one dominant underlying molecular signaling mechanism that is impacted by the riboflavin and UV ( M irasol) PRT process resulting in alterations in PLT quality. The identification of such a target should assist in the development of strategies to ameliorate this negative aspect of an otherwise beneficial and important safety development for transfusion medicine.