HUMAN-IMMUNOGLOBULINS INHIBIT THROMBIN-INDUCED CA2-OXIDE PRODUCTION IN ENDOTHELIAL-CELLS( MOVEMENTS AND NITRIC)

Binding of natural antibodies to endothelial cell plays an important r ole in hyperacute xenograft rejection be tween discordant species. Hum an intravenous immunoglobulins (IVIg) delay this hyperacute rejection, but their mechanisms of action on endothelial cells have to be define d. Here we demonstrate that IVIg dose-dependently prevent thrombin fro m eliciting cytosolic Ca2+ movements and nitric oxide (NO) production in aortic endothelial cells from guinea pig. The Ca2+ response to thro mbin was similarly affected by IVIg whether they were removed or not f rom the incubation medium before stimulation. Pretreatment by rat natu ral antibodies also suppress the thrombin-induced Ca2+ peak correspond ing to Ca2+ release from intracellular stores but stimulate the subseq uent sustained increase in [Ca2+](i) and the release of NO. The action of human intravenous immunoglobulins seems to be selective for the th rombin receptor because they do not affect [Ca2+](i) and NO responses to endothelin-l or thapsigargin. However, these antibodies also suppre ss the first phase of the cytosolic Ca2+ response to ATP, which does n ot release NO under our experimental conditions. These observations ra ise the possibility that IVIg selectively interact with targets locali zed on plasma membrane of endothelial cells for controlling receptor-a ctivated Ca2+ pathways and NO release.