GADD45α is involved in the apoptosis of lymphocytes induced by riboflavin and ultraviolet light

Abstract

These data revealed that RF-PRT effectively inhibited proliferation and induced apoptosis of lymphocytes by promoting GADD45α expression, which subsequently activates p38 and JNK signaling pathways.

Pathogen reduction with riboflavin and ultraviolet light induces a quasi‐apoptotic state in blood leukocytes

“…Caspase expression was not observed in WBCs following UV + R PRT, suggesting that these cells underwent an alternative caspase‐independent apoptotic pathway. Reports using varying doses of UV exposure suggested that WBCs generally undergo conventional apoptosis, that is, caspase activation, up regulation of GADD45α, CD95 (FAS/APO‐1), Bax, and/or p73, and poly–adenosine diphosphate ribose polymerase cleavage . There are, however, reports of caspase‐independent apoptosis occurring in WBCs in response to other stimuli, or in other cell types in response to UV exposure, providing some precedence for our findings .…”

“…Reports using varying doses of UV exposure suggested that WBCs generally undergo conventional apoptosis, that is, caspase activation, up regulation of GADD45α, CD95 (FAS/APO-1), Bax, and/or p73, and poly-adenosine diphosphate ribose polymerase cleavage. 24,29,34,[46][47][48] There are, however, reports of caspaseindependent apoptosis occurring in WBCs in response to other stimuli, or in other cell types in response to UV exposure, providing some precedence for our findings. 22,[48][49][50] Platelets also demonstrated caspase 9 and 3 activity after UVB exposure with riboflavin using the Mirasol system, but differences were observed 5 days after storage.…”

“…Here, we show that UV + R induces apoptotic‐like characteristics in both human and mouse WBCs, including externalization of PS and loss of membrane asymmetry, but unlike canonical apoptosis, caspase expression and chromatin condensation were not apparent. Therefore, PRT with UV + R does not induce conventional apoptosis as originally thought, but instead induces a quasi‐apoptotic state in WBCs . Despite these differences, an allogeneic transfusion of UV + R–treated cells, similar to apoptotic cells, failed to prime enhanced alloantibody responses to secondary allo‐exposure.…”

“…There is some evidence to suggest that the Mirasol system may induce apoptosis. Yang et al 34 described PS exposure in human lymphocytes treated with riboflavin and an in-house source of UVB light, and Asano et al 19 reported elevated PS exposure in rat WBCs following Mirasol treatment. Neither of these studies, however, evaluated indicators of apoptosis beyond PS exposure.…”

“…Therefore, PRT with UV + R does not induce conventional apoptosis as originally thought, but instead induces a quasi-apoptotic state in WBCs. 34 Despite these differences, an allogeneic transfusion of UV + R-treated cells, similar to apoptotic cells, failed to prime enhanced alloantibody responses to secondary allo-exposure.…”