E007 Differential effects of microparticles from human apoptotic T lymphocytes and from human apoptotic monocytes in endothelial cells - 17/04/09
Résumé |
During cell activation or apoptosis, cells release vesicles, also called microparticles (MPs) from the plasma membrane. Since composition of MPs is dependent on cell origin and the type of stimulation, we compared the effects of MPs generated from both apoptotic T lymphocytes and apoptotic monocytes on endothelial function with respect to both nitric oxide (NO) pathway and reactive oxygen species (ROS). MPs were produced by treatment of either human T lymphocytes with the apoptotic agent actinomycin D or human monocytic cell line THP-1 with the apoptotic agent, the etoposide VP-16. Human Eahy 926 endothelial cells were incubated with 10μg/ml MPs for 24h. Apoptotic MPs from human T lymphocytes decreased NO production that was associated with overexpression and phosphorylation of endothelial NOsynthase (eNOS). Also, T lymphocytes MPs enhanced expression of caveolin-1 and decreased its phosphorylation. T lymphocytes MPs enhanced ROS by a mechanism sensitive to xanthine oxidase and P-IkappaBalpha inhibitors. PI3-kinase inhibition reduced the effects of T lymphocytes MPs on eNOS, but not on caveolin-1, whereas it enhanced the effects of MPs on ROS production. Inhibition of MEK reversed eNOS phosphorylation but it had no effect on ROS production induced by T lymphocytes MPs. By contrast, apoptotic MPs from human monocytes increased both NO production and in much less extent ROS. These effects were associated with a decrease of caveolin-1 expression and increased its phosphorylation, without affecting eNOS expression and phosphorylation. The inhibitor of the PI-3kinase, LY294002, reversed the effects of monocyte MPs on caveolin-1 expression but not on its phosphorylation. The MEK1/2 inhibitor, U0126, reversed the decrease of caveolin-1 expression induced by MPs from monocytes. Interestingly, U0126 potentiated ROS production induced by monocyte MPs. Whereas in vivo injection of T lymphocytes MPs in mice impaired endothelial function, apoptotic MPs from human monocytes did not affect endothelium-dependent relaxation. In addition, monocyte MPs were able to promote in vitro angiogenesis. In summary, these results highlight differential effects of apoptotic MPs from different origins by activating diverse multiple pathways related to NO and ROS productions.
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