Regulation of macrophage activation by IL-3. I. IL-3 functions as a macrophage-activating factor with unique properties, inducing Ia and lymphocyte function-associated antigen-1 but not cytotoxicity.
Here we report that IL-3 (also referred to as multi-CSF because of its colony-stimulating activity on a variety of hemopoietic cell lineages) can function as a macrophage-activating factor (MAF). IL-3 was able to regulate the expression of class II MHC Ag and the cellular interaction molecule lymphocyte function-associated Ag-1 on the surface of murine peritoneal exudate cells. The kinetics of IL-3-induced Ia expression appeared to be distinct from that induced by either IFN-gamma, IL-4, or granulocyte-macrophage-CSF. IL-3 was also distinguished from these factors by the finding that it did not induce macrophage tumoricidal activity. In addition to its inherent MAF activities, IL-3 also showed a marked synergy with low doses of LPS (0.05 to 0.5 ng/ml) as well as IFN-gamma in Ia induction. When lymphocyte function-associated Ag-1 expression was evaluated, the effects of these stimuli appeared to be only additive. Although LPS has been shown to inhibit IFN-gamma-induced Ia expression, in our experiments this property of LPS is manifest only when present at doses greater than or equal to 50 ng/ml. At lower concentrations, LPS potentiated both IL-3- and IFN-gamma-induced class II MHC Ag expression. Data presented here also suggest that the synergistic interactions between low doses of LPS and IL-3 are not mediated by known LPS-inducible cytokines of macrophage origin, because rIL-1, TNF-alpha, or IL-6 did not enhance the response to IL-3. Because IL-3 can also participate in the regulation of IL-1 expression, it appears that IL-3 can function as a MAF which selectively regulates the accessory cell characteristics required for Ag presentation, as opposed to the cytolytic functions of the macrophage.
Frendl
G
G
Department of Medicine, Boston University Medical Center, MA.
Beller
D I
DI
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D001685:Biological Factors / Q000494:pharmacology; D016207:Cytokines; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology; D007377:Interleukin-3 / Q000494:pharmacology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D016028:Receptors, Leukocyte-Adhesion / Q000096:biosynthesis*
D000943:Antigens, Differentiation; D001685:Biological Factors; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007377:Interleukin-3; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion; D007371:Interferon-gamma