Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation.

Abstract

In previous reports (1, 2) we demonstrated that Toxoplasma gondii, an obligate intracellular parasite, is susceptible to oxygen intermediates generated by the partial reduction of molecular oxygen. In a cell-free model, toxoplasmas are resistant to superoxide anion (O~-) and hydrogen peroxide (H202), but are readily killed by toxic products of O~-H202 interaction, presumably hydroxyl radical (OH-) and singlet oxygen (102) (1). We also implicated these latter two oxygen intermediates as probable mediators of the toxoplasmastatic and toxoplasmacidal activity of specifically immune peritoneal macrophages (2).The present study extends these observations by examining in parallel the antitoxoplasma activity and oxidative capacity of peritoneal cells stimulated in vivo by inflammatory and immunologic agents, and in vitro by soluble products of sensitized lymphocytes (lymphokines). We have, thus, been able to characterize a spectrum of activated macrophages that differ quantitatively in their production of O~-and H202, and their capacity to carry out an intracellular anti-microbial act. Our observations also reemphasize the importance of macrophage oxygen-dependent antimicrobial mechanisms in both the in vivo and in vitro activated state. Materials and MethodsParasites. The virulent RH strain and the nonvirulent Pe strain of Toxoplasma gondii were maintained and harvested as previously reported (1). RH strain toxoplasma trophozoites were used to infect cultivated macrophages, whereas Pe strain brain cysts were used to produce chronically infected toxoplasma immune mice (2).Macrophages. Normal macrophages were obtained from female NCS mice (The Rockefeller University, New York). Toxoplasma-immune macrophages (IM) 1 and immune-boosted macrophages (IB) were from NCS mice infected 3-8 wk before the Pe brain cysts. Immune-boosted mice received 5 × 106 heat-killed RH toxoplasma trophozoites intraperitoneally 3 d before harvest (2). Other NCS mice were injected intravenously or intraperitoneally with 2 × 107 * Supported by grants 1 732 GM-07247 and AI-07012 from the U. S. Public I~tealth Service, and The Rockefeller Foundation Grant GAllS 7716.:~ Present address: Cornell University Medical College, New York 10021. 'Abbreviations used in this paper: BCG, Bacille Calmette-Gu~rin, Con A, concanavalin A; DABCO, diazabicyclooctane; D20HIFBS, Dulbecco's medium containing 20% heat-inactivated FBS, penicillin, and streptomycin; FBS, fetal bovine serum; HIB, heart infusion broth; IB, toxoplasma immune-boosted; IM, toxoplasma-immune; NBT, nitroblue tetrazolium; PBS, phosphate-buffered saline; PMA, phorbol myrisrate acetate; PP, proteose peptone; SOD, superoxide dismutase; THIO, thioglycollate. 1596J. ExP. MED.

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“…parvum is well recognized as a nonspecific stimulator of the immune system. Peritoneal macrophages obtained from mice injected with C. parvum exhibit increased tumoricidal and antimicrobial activities in vitro (22,23). Macrophages are known to recognize and ingest immune complexes via their Fc receptor for IgG.…”

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