EFFECTS OF MYCOPLASMA-FERMENTANS ON THE MYELOMONOCYTIC LINEAGE - DIFFERENT MOLECULAR ENTITIES WITH CYTOKINE-INDUCING AND CYTOCIDAL POTENTIAL

Mycoplasma fermentans is a mycoplasma species that has been accused of serving as a cofactor of AIDS development, Here, we show that M, ferm entans affects the function of human monocytes and myelomonocytic cell lines on at least two different levels, Heat-inactivated mycoplasma p articles induce inflammatory cytokines such as IL-1, IL-6, and TNF in monocytes, as well as in THP-1 cells, Moreover, M, fermentans induces IL-10 (but not IL-12) in freshly isolated human monocytes, The cytokin e-inducing effect is mediated by lipid-associated molecules, In additi on, we have detected a novel biologic activity that resides in the non lipid-associated protein fraction of M, fermentans (approximate molecu lar mass: 15 to 30 kDa) and that has a cytocidal effect on nondifferen tiated myelomonocytic cell lines (U937 cells, HL-60 cells), as well as on actinomycin-D-sensitized monocytes, Death is accompanied by oligon ucleosomal DNA fragmentation and loss of chromosomal DNA, U937 and HL- 60 cells fail to produce cytokines and rather undergo cell death in re sponse to heat-inactivated M, fermentans, provided that they are kept in a relatively undifferentiated stage, Whereas the cytokine-inducing activity is a general feature of many mycoplasma species, it appears t hat only a restricted panel of mycoplasma species exert a cell death-i nducing activity, In addition to M, fermentans strains, Mycoplasma pen etrans, another hypothetical cofactor of AIDS, possesses a cytocidal a ctivity, This does not apply to other mycoplasma species, including pa thogenic ones such as Mycoplasma pneumoniae and Ureaplasma urealyticum , The cell death-inducing effect of M, fermentans is not mediated by c ytokines and obeys different principles than TNF-cu-mediated apoptosis , Thus, in contrast to TNF-a-induced death, it is not accompanied by a decrease in the mitochondrial transmembrane potential and is not inhi bited by preincubation with the antioxidant drug N-acetylcysteine, In synthesis, it appears that certain AIDS-associated mycoplasma species perturb the function and/or generation of cells from the myelomonocyti c lineage via several distinct pathways.