Induction of antitumor activity in macrophages by mycoplasmas in concert with interferon

Abstract

The in vitro growth of tumor cells infected with mycoplasmas was suppressed by macrophages pretreated with interferon (IFN), but the growth of mycoplasma-free tumor cells was not suppressed. Pretreatment of macrophages with IFN plus mycoplasmas or their soluble factors either simultaneously or sequentially, IFN first and mycoplasmas second, but not in the reverse order, was effective in activating macrophages to suppress the growth of mycoplasma-free tumor cells. Macrophages from C3H/HeJ mice (which respond only slightly to lipopolysaccharide) were activated by IFN plus mycoplasmas or their soluble factor, and their action was not influenced by the addition of a lipopolysaccharide-neutralizing agent, polymyxin B. These results suggest that the macrophage-activating agent in mycoplasmas does not mimic lipopolysaccharide. The administration of mycoplasmas plus IFN to mice with ascitic or solid tumors resulted in the reduction of tumor growth. The survival rate of tumor-bearing mice was improved by the administration of mycoplasmas, and this was synergistically enhanced by the addition of IFN. These results indicate (a) that mycoplasmas can be useful as a biological response modifier, and (b) that care should be taken to prevent contamination with mycoplasmas in experiments on macrophage activation.

Macrophage-activating factor extracted from mycoplasmas

“…We documented previously that various species of mycoplasmas were able to activate M0 primed by IFNct to make them antitumor effector cells [18]. In this study, we have shown that chicken mycoplasmas, as well as lipopolysaccharide, activate M0 in concert with IFNy, The M0-activating capacity of mycoplasmas is quite resistant to heat, acid, or trypsin, and relatively labile in alkaline solutions.…”

“…We documented in a previous paper that the host resistance to tumors was enhanced in mice receiving different species of mycoplasmas and interferon (IFN) c~ [18]. Our in vitro investigation demonstrated that mycoplasmas, whether tumor-cell-bound or in free form, play a role, as a second signal for macrophages (M0) primed by IFN~ as a first signal, in the activation of M0 to acquire tumoricidal capacity.…”

From Bench to Cageside: Risk Assessment for Rodent Pathogen Contamination of Cells and Biologics

“…Because Mycoplasma contamination of cell lines can wreak havoc on cellular studies, high-quality laboratories periodically test cultures for this pathogen. Identification of Mycoplasma in cell lines is also of concern to those who perform in vivo studies because of the well-documented effects of contamination on cell growth and the immune system (Uno et al 1990; Ushio et al 1995). Caution is further warranted as the administration of Mycoplasma-contaminated cells to immunocompromised mice (and other strains) can result in sepsis and other clinical illnesses (Dodds et al 2003).…”

Molecular Biology and Pathogenicity of Mycoplasmas

“…Mycoplasmas activate macrophages by a mechanism different from that used by LPS inasmuch as they act upon macrophages from LPSnonresponsive C3H/HeJ mice (263,299,413,414,443,463). The effects of mycoplasmas were not inhibited by polymyxin B (463,480) and synergized with LPS in triggering TNF-␣ production by macrophages from LPS-responsive mice (413,414). It appears that while mycoplasmas evade phagocytosis, they interact with mononuclear and polymorphonuclear phagocytes and exert either suppressive or stimulating effects upon them by a combined action of direct and indirect cytokine-mediated effects.…”

“…Studies to elucidate the mechanisms by which mycoplasmas trigger macrophage tumoricidal activity have clearly established that the organisms induced the production of TNF-␣ that subsequently played a major role in toxicity toward tumor cells (12,149,413,414). Mycoplasmas activate macrophages by a mechanism different from that used by LPS inasmuch as they act upon macrophages from LPSnonresponsive C3H/HeJ mice (263,299,413,414,443,463). The effects of mycoplasmas were not inhibited by polymyxin B (463,480) and synergized with LPS in triggering TNF-␣ production by macrophages from LPS-responsive mice (413,414).…”