Effect of granulocyte-macrophage colony stimulating factor on endothelial antigenicity.
We have investigated if recombinant granulocyte-macrophage colony stimulating factor (GM-CSF), alone or in concert with recombinant gamma 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 gamma 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-isoquinolinesulfonamide (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 gamma GM-CSF, HA 1004 as well as indomethacin abolished the inhibitory effect of GM-CSF on interferon gamma-induced class I expression. The results suggest that GM-CSF diminishes effect of interferon gamma 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.
Leszczynski
D
D
Transplantation Laboratory, University of Helsinki, Finland.
Häyry
P
P
D000818:Animals; D003115:Colony-Stimulating Factors / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000276:immunology*; D005786:Gene Expression Regulation / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D009206:Myocardium / Q000276:immunology; D011453:Prostaglandins / Q000502:physiology; D047428:Protein Kinase Inhibitors; D051381:Rats; D011994:Recombinant Proteins; D013449:Sulfonamides
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D015395:Histocompatibility Antigens Class I; D007546:Isoquinolines; D011453:Prostaglandins; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D013449:Sulfonamides; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D000242:Cyclic AMP; D006152:Cyclic GMP