Effect of granulocyte-macrophage colony stimulating factor on endothelial antigenicity

Abstract

We have investigated if recombinant granulocyte-macrophage colony stimulating factor (GM-CSF), alone or in concert with recombinant γ interferon, affects the endothelial cell expression of class I major histocompatibility complex antigen. Results obtained show that the GM-CSF increases class I expression on the endothelial cell in a time- and dose-dependent manner. The effect of interferon γ on class I expression is diminished in the presence of GM-CSF, cAMP, or prostaglandin E2, but is increased in the presence of cGMP. N-(2-guanidinoethyl)-5-isoquinolonesulfonamide (HA 1004), an inhibitor of cAMP- and cGMP-dependent protein kinases, abolished GM-CSF-induced class I expression, while indomethacin increased it. When added to the endothelial cell cultures together with interferon γ GM-CSF, HA 1004 as well as indomethacin abolished the inhibitory effect of GM-CSF on interferon γ-induced class I expression. The results suggest that GM-CSF diminishes effect of interferon γ on class I major histocompatibility complex expression on the endothelial cell by inducing production of rostacyclin. This, in turn, induces cAMP as a second messenger, which then leads to the events inhibiting expression of class I major histocompatibility complex antigen.