Components of the protein kinase C pathway induce Ia expression after injection into macrophages.
Macrophages are activated by a variety of microbial and cytokine stimuli. One feature of activation is the induction of class II Ag (Ia) on the cell surface. To understand the intracellular events that occur during activation, we investigated various agents with intracellular activities, and examined their effects on the induction of Ia. We first noted that several agents that activate protein kinase C (PKC) induced Ia, and that several inhibitors of PKC inhibited Ia induction by IFN-gamma. To directly test whether PKC induced Ia, we microinjected normal peritoneal macrophages with this enzyme and other intracellular mediators, then examined Ia expression. We observed that injection of PKC itself, or of other intracellular proteins thought to participate in the PKC pathway (Ras or phospholipase C gamma) strongly induced Ia expression. The Ia-inducing activity of transforming Ras protein was blocked by kinase inhibitor treatment of cells, suggesting that Ras signal transduction requires kinase activity. On the other hand, components of the protein kinase A pathway (phospholipase A2 and protein kinase A itself) did not induce Ia. Thus, the PKC pathway can control expression of macrophage surface Ia, possibly by regulating the genes of the MHC, and may play many other roles in the activation of macrophages.
Smith
M R
MR
Biological Carcinogenesis and Development Program, DynCorp, Frederick, MD.
Ramsburg
E A
EA
Kung
H F
HF
Durum
S K
SK
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008845:Microinjections; D009281:Naphthalenes; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D015398:Signal Transduction; D019311:Staurosporine; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D000470:Alkaloids; D004075:Diglycerides; D000949:Histocompatibility Antigens Class II; D007546:Isoquinolines; D009281:Naphthalenes; D011083:Polycyclic Compounds; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000001:Calcimycin; D007371:Interferon-gamma; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011494:Protein Kinases; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D016283:Proto-Oncogene Proteins p21(ras); D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate