Abstract
Binding of natural antibodies to endothelial cell plays an important role in hyperacute xenograft rejection between discordant species. Human intravenous immunoglobulins (IVIg) delay this hyperacute rejection, but their mechanisms of action on endothelial cells have to be defined. Here we demonstrate that IVIg dose-dependently prevent thrombin from eliciting cytosolic Ca2+ movements and nitric oxide (NO) production in aortic endothelial cells from guinea pig. The Ca2+ response to thrombin was similarly affected by IVIg whether they were removed or not from the incubation medium before stimulation. Pretreatment by rat natural antibodies also suppress the thrombin-induced Ca2+ peak corresponding to Ca2+ release from intracellular stores but stimulate the subsequent sustained increase in [Ca2+]i and the release of NO. The action of human intravenous immunoglobulins seems to be selective for the thrombin receptor because they do not affect [Ca2+]i and NO responses to endothelin-1 or thapsigargin. However, these antibodies also suppress the first phase of the cytosolic Ca2+ response to ATP, which does not release NO under our experimental conditions. These observations raise the possibility that IVIg selectively interact with targets localized on plasma membrane of endothelial cells for controlling receptor-activated Ca2+ pathways and NO release.
Highlights
Binding of natural antibodies to endothelial cell plays an important role in hyperacute xenograft rejection between discordant species
Incubation of cells for 5 min at 37 °C with 10 mg/ml intravenous immunoglobulins (IVIg) or rat IgG followed by a washing to remove unbound antibodies from the incubation medium did not change basal [Ca2ϩ]i values (Fig. 1, B and C) but altered the Ca2ϩ response to thrombin
Human and rat natural antibodies did not modify per se the cytosolic Ca2ϩ level in aortic endothelial cells from guinea pig but did modulate the Ca2ϩ movements elicited by thrombin, a protease generated at sites of vascular injury
Summary
Binding of natural antibodies to endothelial cell plays an important role in hyperacute xenograft rejection between discordant species. The present study was undertaken to investigate the action of IVIg and rat natural antibodies (IgG) on cytosolic Ca2ϩ movements and NO production elicited by thrombin in aortic endothelial cells from guinea pig. Incubation of cells for 5 min at 37 °C with 10 mg/ml IVIg or rat IgG followed by a washing to remove unbound antibodies from the incubation medium did not change basal [Ca2ϩ]i values (Fig. 1, B and C) but altered the Ca2ϩ response to thrombin.
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