Regulation of murine macrophage function by IL-4. I. Activation of macrophages by a T-T cell hybridoma is due to IL-4.
A T-cell hybridoma produced by fusion of concanavalin A-stimulated murine splenocytes produced a factor (MAFH) capable of activating tumoricidal capacity by responsive murine peritoneal macrophages. Macrophages treated with the MAFH required an additional trigger signal of bacterial lipopolysaccharide (LPS) for maximal activity. In contrast to interferon-gamma (IFN gamma), which induced tumoricidal activity against all tumor cells tested, MAFH only induced macrophage-mediated kill of the BI6P51 and 168 lines, and not of the P815 or B16BL6 lines. An identical pattern of tumoricidal activity was obtained by treating macrophages with recombinant interleukin-4 (IL-4). The active moiety of MAFH appeared to be IL-4 as (i) monoclonal antibody against IL-4 blocked MAFH, but not IFN gamma, activity, and (ii) the T-cell hybridoma contained large amounts of mRNA for IL-4 and no detectable mRNA for IFN gamma (as determined by Northern dot analysis). The pattern of tumoricidal activity observed may be due to an IL-4 mediated enhancement of tumor necrosis factor production by LPS-triggered macrophages.
Somers
S D
SD
Department of Human Anatomy, School of Medicine, University of California, Davis 95616.
Erickson
K L
KL
D000818:Animals; D005260:Female; D006825:Hybridomas / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007378:Interleukins; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma