Gamma-interferon regulates vascular smooth muscle proliferation and Ia antigen expression in vivo and in vitro.
A significant fraction of the arterial smooth muscle cells in atherosclerotic plaques and injury-induced intimal thickenings express class II major histocompatibility complex (Ia) antigens. This might be the consequence of gamma-interferon secretion by T lymphocytes also present in these lesions. We have therefore analyzed the effects of gamma-interferon on cultured rat aortic smooth muscle cells. Recombinant gamma-interferon inhibited smooth muscle proliferation in vitro in a dose-response relation; inhibition was detectable down to a concentration of 1 unit/ml. In similar concentrations, gamma-interferon also induced Ia expression by the cells. This suggested that Ia antigens might be selectively expressed by nonproliferating smooth muscle cells. In vivo, there was a strong negative correlation between Ia expression and 3H-thymidine labeling of smooth muscle cells in intimal thickenings induced by balloon catheter injury. In rats receiving continuous infusions of 3H-thymidine for two weeks after injury, Ia-positive 3H-positive cells had undergone fewer rounds of replication than Ia-negative ones. This indicates that Ia-expression both in vivo and in vitro is associated with a reduced proliferative capacity. These results suggest that gamma-interferon, a secretory product of activated T lymphocytes, acts as a natural regulator of smooth muscle cell growth and Ia expression in injury-induced intimal thickenings and atherosclerotic plaques.
D000818:Animals; D001696:Biomechanical Phenomena; D020212:Carotid Artery Injuries; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D013936:Thymidine / Q000378:metabolism; D014945:Wound Healing
D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D007371:Interferon-gamma; D013936:Thymidine