Macrophages (Mφ) from three mouse strains with genetically distinct Mφ 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-β) that strongly increased the tumoricidal capacity of Mφ from nondefective C3H/HeN mice. Nevertheless, the tumoricidal deficits of Mφ from the defective strains did not affect their suppressive capacity on Con A-induced lymphoproliferation, nor their ability to react to IFN-β by decreasing suppressive activity. In fact, natural suppressive activity and IFN-β-induced changes in the suppression of Mφ from C3H/HeJ, A/J, and P/J mice were highly comparable to those of C3H/HeN Mφ, thus stressing the dossociation between the mechanisms governing Mφ suppression and M3F tumoricidal activity. Analysis of the modulation by MAF and IFN-β of Mφ ability to release the oxygen metabolites O2 - and H2O2, molecules possibly involved in the effector mechanism of both Mφ 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 Mφ tumoricidal activity was observed. The ability of MAF- and IFN-β-treated Mφ to produce PGE, a molecule of major importance in Mφ-mediated suppression and possibly involved also in the regulation of Mφ tumoricidal activity, again paralleled Mφ suppressive capacity. Thus, the mechanisms controlling Mφ antitumor activity appeared to be clearly distinct from those involved in Mφ suppression.
|Number of pages||7|
|Journal||Journal of Immunology|
|Publication status||Published - 1983|
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