Dissociation between macrophage tumoricidal capacity and suppressive activity: analysis with macrophage-defective mouse strains.
Macrophages (M phi diameter) from three mouse strains with genetically distinct M phi diameter deficits (C3H/HeJ, A/J, and P/J) were unable to develop high cytolytic and cytotoxic activity against tumor cells in vitro when exposed to agents (MAF and IFN-beta) that strongly increased the tumoricidal capacity of M phi diameter from nondefective C3H/HeN mice. Nevertheless, the tumoricidal deficits of M phi diameter from the defective strains did not affect their suppressive capacity on Con A-induced lymphoproliferation, nor their ability to react to IFN-beta by decreasing suppressive activity. In fact, natural suppressive activity and IFN-beta-induced changes in the suppression of M phi diameter from C3H/HeJ, A/J, and P/J mice were highly comparable to those of C3H/HeN M phi diameter, thus stressing the dissociation between the mechanisms governing M phi diameter suppression and M phi diameter tumoricidal activity. Analysis of the modulation by MAF and IFN-beta of M phi diameter ability to release the oxygen metabolites O2- and H2O2, molecules possibly involved in the effector mechanism of both M phi diameter cytotoxicity and suppression, revealed a close correlation with the patterns of suppressive activity in both nondefective and defective strains. In contrast, no correlation between the production of oxygen-reactive species and M phi diameter tumoricidal activity was observed. The ability of MAF- and IFN-beta-treated M phi diameter to produce PGE, a molecule of major importance in M phi diameter-mediated suppression and possibly involved also in the regulation of M phi diameter tumoricidal activity, again paralleled M phi diameter suppressive capacity. Thus, the mechanisms controlling M phi diameter antitumor activity appeared to be clearly distinct from those involved in M phi diameter suppression.
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D007108:Immune Tolerance; D007370:Interferon Type I / Q000502:physiology; D008222:Lymphokines / Q000502:physiology; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D011458:Prostaglandins E / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D013481:Superoxides / Q000096:biosynthesis
D007370:Interferon Type I; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D011458:Prostaglandins E; D013481:Superoxides; D006861:Hydrogen Peroxide