title: Comparison of transforming growth factor-beta and a macrophage- deactivating polypeptide from tumor cells. Differences in antigenicity and mechanism of action.
abstract: A factor in medium conditioned by mouse tumor cells was shown previously to suppress the capacity of mouse peritoneal macrophages to undergo a respiratory burst and to kill protozoal pathogens (macrophage deactivation factor, MDF). Recently, pure transforming growth factor-beta (TGF-beta) proved to be a potent macrophage deactivator as well. Two lines of evidence suggest that MDF is not identical with TGF-beta. First, rabbit anti-TGF-beta IgG neutralized the respiratory burst-suppressing activity of TGF-beta without affecting the bioactivity of MDF, even when the latter was treated with acid to activate potentially latent TGF-beta. Second, in contrast to MDF, which decreases the affinity of the NADPH oxidase for NADPH, permeabilized macrophages that had been deactivated with TGF-beta displayed the same Km and Vmax of the oxidase as activated macrophages. As with MDF, TGF-beta had no effect on two other potential control points over the secretion of respiratory burst products, namely, hydrogen peroxide catabolism or glucose uptake. Finally, neither MDF nor TGF-beta affected the extent or affinity of binding of phorbol diesters to macrophages, the activity or cofactor requirements for protein kinase C, or the ability of protein kinase C to translocate quantitatively from cytosol to membrane fractions in response to phorbol diesters. Thus, 1) MDF is not identical with TGF-beta, and 2) in contrast to the activation or deactivation of macrophages by numerous other agents, TGF-beta regulates macrophage respiratory burst capacity at a level other than the apparent affinity of the oxidase for its substrate.
authors.affiliation: Beatrice and Samuel A. Seaver Laboratory, Cornell University Medical College, New York 10021.
authors.forename: S
authors.initials: S
authors.lastname: Tsunawaki
authors.forename: M
authors.initials: M
authors.lastname: Sporn
authors.forename: C
authors.initials: C
authors.lastname: Nathan
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000302:isolation & purification; D001692:Biological Transport / Q000187:drug effects; D015815:Cell Adhesion Molecules; D003847:Deoxyglucose / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology; D007700:Kinetics; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D015291:Transforming Growth Factors / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000941:Antigens; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D007106:Immune Sera; D007166:Immunosuppressive Agents; D009363:Neoplasm Proteins; D015291:Transforming Growth Factors; D003847:Deoxyglucose; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011493:Protein Kinase C