UV irradiation of lymphocytes triggers an increase in intracellular Ca2+ and prevents lectin-stimulated Ca2+ mobilization: evidence for UV- and nifedipine-sensitive Ca2+ channels.
UV irradiation induces in vitro and in vivo immunosuppression. Because mobilization of intracellular calcium ([Ca2+]i) represents a central step in cell activation and immune response, we investigated the effect of UV irradiation on Ca2+ homeostasis. Using indo-1 and cytofluorometry, [Ca2+]i kinetics in UVC- or UVB-exposed human peripheral blood leukocytes (PBL) and Jurkat cells were determined in parallel with functional assays. Increases in [Ca2+]i were observed within 2-3 h of irradiation; these increases were UV-dose dependent and reached maxima of 240% and 180% above baseline level (130 nM) for UVB and UVC, respectively. The UV-induced [Ca2+]i rise was predominantly due to influx of extracellular calcium, and it was more pronounced in T than in non-T cells. Concurrent with [Ca2+]i shifts following UV treatment, there was a loss of ability to respond to phytohemagglutinin (PHA) or to proliferate or stimulate in mixed leukocyte culture. This loss of function appeared to be related not only to UV-induced calcium shifts, but also to effects of UV irradiation on the plasma membrane. No [Ca2+]i mobilization was induced by gamma irradiation, and gamma-irradiated cells showed a normal [Ca2+]i increase in response to PHA. UV-induced Ca2+ flux into the cells was blocked by nifedipine. These data indicate that UV and gamma irradiation have different effects on lymphocyte membranes and suggest that a disruption of Ca2+ homeostasis may be involved in UV-induced lymphocyte inhibition. The data suggest, furthermore, the presence of Ca2+ channels in lymphocyte membranes that are sensitive to UV irradiation and Ca2+ channel blockers such as nifedipine.
Spielberg
H
H
Vincent T. Lombardi Cancer Research Center, Georgetown University School of Medicine, Washington, DC.
June
C H
CH
Blair
O C
OC
Nystrom-Rosander
C
C
Cereb
N
N
Deeg
H J
HJ
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D007959:Lymphocyte Culture Test, Mixed; D016131:Lymphocyte Subsets / Q000528:radiation effects*; D009543:Nifedipine / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D015220:Calcium Channels; D010835:Phytohemagglutinins; D009543:Nifedipine; D002118:Calcium