Synergism between human recombinant monocyte chemotactic and activating factor and lipopolysaccharide for activation of antitumor properties in human blood monocytes.
Monocyte chemotactic and activating factor (MCAF) is an important mediator of monocyte recruitment to sites of chronic inflammation and neoplasia. In the present study, we determined whether MCAF can also enhance the activation of tumoricidal capacity of monocytes. Human monocytes incubated with MCAF and subthreshold concentrations of lipopolysaccharide (LPS) exhibited synergistic tumoricidal activity against allogeneic A375 melanoma cells, irrespective of their metastatic potential. The sequence of MCAF and LPS treatment was crucial. Monocytes treated first with MCAF for 4 h and then with LPS for 18 h were highly cytotoxic to the melanoma cells, whereas monocytes first treated with LPS and then with MCAF were not. Treatment of monocytes with MCAF and LPS also significantly increased production of tumor necrosis factor. These data suggest that like interferon-gamma, MCAF can prime human monocytes to respond to LPS. Interleukin-8, a chemokine for neutrophils, did not enhance the monocytes' LPS-triggered tumoricidal response. Collectively, these data show that MCAF can influence the recruitment and tumoricidal activation of blood monocytes. Therefore, MCAF may be an important mediator of tumor regression.
Singh
R K
RK
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Fidler
I J
IJ
D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008207:Lymphatic Metastasis; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma