Mechanisms by which oxidative injury inhibits the proliferative response of human lymphocytes to PHA. Effect of the thiol compound 2-mercaptoethanol.
The use of normobaric exposure to O2 as a model for in vitro oxidative injury prevented phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) from undergoing the G0 to G1 transition, but 5 x 10(-6) M 2-mercaptoethanol (2-ME) almost protected the cells from this blockade. The percentage of cells with IL-2 and transferrin-receptors was reduced by the O2 exposure and, like the cell cycle transition, was protected by 2-ME against oxidative injury. By contrast, IL-2 recovery in the supernatants of O2-exposed PHA-stimulated PBMC was enhanced. This enhancement may be due partly to the reduced IL-2 consumption caused by the decreases in IL-2 receptor expression and in proliferation. On the other hand, IL-2 recovery in the supernatants of O2-treated PBMC was always enhanced compared to the IL-2 control recovery after DNA synthesis was blocked in G1/S by mitomycin c, and the G0/G1 transition was protected by 2-ME. Furthermore, PHA-stimulated monocytes exposed to O2 produced more IL-1 than control cells. This enhanced IL-1 production was not modified by 2-ME. These results suggest that oxidative injury reduces the proliferation of PBMC by interfering with the cellular events that lead to the transition from the G0 to the G1 phase of the cell cycle. The protective effects of 2-ME suggest that thiol compounds have a critical role in the early events of the cell cycle. By contrast, exposure to O2 induced increases in the production of both IL-1 and IL-2 that may not be related to alterations in the thiol status of the cell.
Gougerot-Pocidalo
M A
MA
INSERM U. 294, Chu Bichat, Paris, France.
Fay
M
M
Roche
Y
Y
Chollet-Martin
S
S
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007378:Interleukins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008623:Mercaptoethanol / Q000494:pharmacology*; D010100:Oxygen / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology
D007378:Interleukins; D010835:Phytohemagglutinins; D008623:Mercaptoethanol; D010100:Oxygen