Tumor necrosis factor and IL-1 associated with plasma membranes of activated human monocytes lyse monokine-sensitive but not monokine-resistant tumor cells whereas viable activated monocytes lyse both.
The purpose of our study was to determine some of the mechanisms involved in macrophage-mediated lysis of tumorigenic cells. A375 human melanoma cells (A375-R) resistant to lysis mediated by TNF and IL-1 were selected from the TNF- and IL-1-sensitive A375 parental melanoma cells subsequent to continuous (2 mo) exposure to rTNF. Peripheral blood monocytes isolated by centrifugal elutriation from healthy donors were incubated with rIFN-gamma and muramyl dipeptide, with a lipoprotein derived from Escherichia coli (CG-31362) or with LPS for 24 h. These activated monocytes lysed both the A375 (monokine-sensitive) and A375-R (monokine-resistant) melanoma cells. Activated tumoricidal macrophages fixed in 2% paraformaldehyde lysed only the TNF- and IL-1-sensitive A375 cells. These fixed monocytes contained both IL-1 and TNF activities as determined by D10 cell proliferation and L929 cytolysis assays, respectively. Nearly identical results were obtained with preparations of plasma membranes from activated human monocytes. Anti-IL-1 and/or anti-TNF sera neutralized the cytolysis of tumor cells mediated by free monokines, by fixed monocytes, or by plasma membrane preparations. In contrast, anti-TNF and/or anti-IL-1 sera did not inhibit tumor cell lysis by viable activated monocytes. We conclude that IL-1 and TNF molecules associated with the plasma membranes of activated monocytes mediate lysis of susceptible target cells. However, because activated monocytes lysed IL-1-and TNF-resistant target cells, molecules other than these monokines must also be involved in the antitumor activity of monocytes.
Ichinose
Y
Y
Department of Cell Biology, University of Texas, Houston 77030.
Bakouche
O
O
Tsao
J Y
JY
Fidler
I J
IJ
D002458:Cell Fractionation; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005557:Formaldehyde; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects; D007375:Interleukin-1 / Q000276:immunology* / Q000502:physiology; D007958:Leukocyte Count; D008262:Macrophage Activation / Q000187:drug effects; D008545:Melanoma / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000502:physiology; D009500:Neutralization Tests; D011108:Polymers; D011994:Recombinant Proteins / Q000276:immunology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000502:physiology
D007106:Immune Sera; D007375:Interleukin-1; D011108:Polymers; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; C003043:paraform