Biosynthesis of macrophage activation factor.
Splenic lymphocytes from BCG-immunized mice were cultured with PPD for 72 hrs. The proteins secreted by these cells activate peritoneal macrophages to kill TU-5 mouse kidney cells. The fraction whose molecular weight falls between 67K and 50K exhibits most of the macrophage stimulating activity. However, lymphokine protein isolated from cultures of splenic lymphocytes harvested from iron-deficient mice showed decreased macrophage stimulating activity. These results further demonstrate the requirement for iron in lymphokine-dependent macrophage cytotoxic activity. Evidence is presented to suggest that the lymphokine fraction which induces tumoricidal activity binds first to a specific site on the surface of the macrophage membrane and then induces protein synthesis. In addition, the lymphokine proteins isolated from iron deficient or unstimulated spleen cultures neither bind to nor induce tumoricidal activity in macrophages. The binding of lymphokine to macrophages seems to be specific since no significant binding occurred to several other cell lines. The binding is saturable and reversible since the bound protein can be displaced by unlabelled lymphokines or xylose at concentration of 0.1M. The SDS gel analysis of macrophage membrane proteins newly synthesized in response to lymphokine showed several proteins with the different mol. wt. but major protein peaks approximately at 55K. The significance of induction of protein synthesis in macrophages by lymphokine is discussed.
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D007668:Kidney; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008222:Lymphokines / Q000096:biosynthesis* / Q000302:isolation & purification; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009163:Mycobacterium bovis / Q000276:immunology
D008222:Lymphokines; D016215:Macrophage-Activating Factors