Psoralen and Ultraviolet A Light Treatment Directly Affects Phosphatidylinositol 3-Kinase Signal Transduction by Altering Plasma Membrane Packing

Abstract

Edited by George CarmanPsoralen and ultraviolet A light (PUVA) are used to kill pathogens in blood products and as a treatment of aberrant cell proliferation in dermatitis, cutaneous T-cell lymphoma, and graftversus-host disease. DNA damage is well described, but the direct effects of PUVA on cell signal transduction are poorly understood. Because platelets are anucleate and contain archetypal signal transduction machinery, they are ideally suited to address this. Lipidomics on platelet membrane extracts showed that psoralen forms adducts with unsaturated carbon bonds of fatty acyls in all major phospholipid classes after PUVA.

High platelet content can increase storage lesion rates following Intercept pathogen inactivation primarily in platelet concentrates prepared by apheresis

“…Experimental research has demonstrated that quality control parameters of Intercept pathogen‐inactivated platelets generally are within predefined ranges but with a significant impact on in vitro function . This is caused by irreversible changes in the platelet plasma membrane which affect subsequent intracellular signal transduction . Clinical studies have demonstrated significantly lower corrected count increments at 1 and 24 h, shorter transfusion intervals and increased transfusions of Intercept‐treated platelets compared to standard concentrates .…”

Standardization of regimens in Narrowband UVB and PUVA in early stage mycosis fungoides: position paper from the Italian Task Force for Cutaneous Lymphomas

“…In vitro experiments on circulating lymphocytes demonstrated that apoptotic process is observable from 12 h after irradiation, increasing at 24 and 48 h and being directly proportional to UVA and 8‐MOP doses . Moreover, some recent findings have identified a systemic effect on inflammation by the modulation of pro‐inflammatory cytokines and the inhibition of the signal transduction in the phosphatidylinositol 3‐kinase (PI3K) pathway …”

“…35,36 Moreover, some recent findings have identified a systemic effect on inflammation by the modulation of pro-inflammatory cytokines 37 and the inhibition of the signal transduction in the phosphatidylinositol 3-kinase (PI3K) pathway. 38 The theoretical advantages of PUVA over NB-UVB are in terms of reduced erythemogenic activity and better penetration towards deeper dermal layers, up to hypoderma and deepest adnexal structures. 11 This has been empirically confirmed by studies comparing efficacy among PUVA and NB-UVB in patients with MF.…”

α‐Synuclein concentration increases over time in plasma supernatant of single donor platelets

“…24 In regard to pathogen reduction technology implementation which seeks to make the platelet inventory safer for recipients, it should be of interest that use of psoralen and ultraviolet A light therapy on platelets inhibits signal transduction and normal docking of liposomes onto α-synuclein. 25 These findings suggest that looking at α-synuclein concentration increases as a surrogate biomarker of changes to platelet biology in response to such technology may prove essential to determine if use of pathogen reduction leads to changes in platelets' health. Similarly, in light of the current increased interest in using cold-stored platelets, [26][27][28] it would also be of interest to establish whether α-synuclein concentration changes can also be indicative of platelet health in this setting as well.…”