Effects of IL-4 on macrophage functions: increased uptake and killing of a protozoan parasite (Trypanosoma cruzi).
We studied whether interleukin-4 (IL-4) could modulate two macrophage functions relevant to their microbicidal activity (uptake and killing), using non-invasive [amastigote (AMA)] forms of the protozoan parasite Trypanosoma cruzi. Treatment of cultures of mouse resident peritoneal macrophages (MPM) with the supernatant of cultures of cells transfected with IL-4 cDNA increased both the capacity of the MPM to take up the organisms and the rate of intracellular killing with respect to MPM mock-treated with medium alone. The presence in the medium of a monoclonal antibody specific for IL-4 during MPM treatment inhibited both effects, pointing to recombinant IL-4 (rIL-4) as the active principle in the supernatant. Kinetic studies revealed that at least a 24-hr pretreatment of the MPM with the rIL-4-containing supernatant was required for these effects to be produced. The rate of intracellular parasite killing was also significantly increased when the rIL-4 treatment was applied after AMA ingestion by MPM. This result confirmed that MPM could be activated by rIL-4 for greater intracellular killing and showed that this enhancement was not necessarily dependent on the initial rIL-4-mediated increase in parasite load. The use of scavengers of reactive oxygen reduction intermediates indicated that hydrogen peroxide, superoxide anion and singlet oxygen, but apparently not hydroxyl radicals, were involved in parasite killing modulated by rIL-4. These results document for the first time the capacity of IL-4 to enhance the microbicidal activity of macrophages and suggest that this lymphokine might play a role in host defence against T. cruzi infection.
Wirth
J J
JJ
Department of Microbiology and Public Health, Michigan State University, East Lansing 48824-1101.
Kierszenbaum
F
F
Zlotnik
A
A
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D006639:Histidine / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000276:immunology*
D007378:Interleukins; D015847:Interleukin-4; D006639:Histidine; D002374:Catalase; D013482:Superoxide Dismutase