Mycoplasma fermentans-derived high-molecular-weight material induces interleukin-6 release in cultures of murine macrophages and human monocytes

Abstract

A Mycoplasma fermentans-derived high-molecular-weight material (MDHM) is described which causes differentiation of concanavalin A-stimulated CBA/J or C57BL/6 mouse thymocytes to cytolytic effector T cells (CTLs). The effect of MDHM was inhibited by addition of monoclonal anti-interleukin-6 (IL-6) antibody. It could also be abolished after removal of adherent cells. However, adherent cell-depleted thymocytes could still form CTLs after addition of IL-6. The action of MDHM could thus be explained by the capacity of MDHM to stimulate IL-6 release from adherent cells. MDHM was active on macrophages from CBA/J and C3H/HeJ endotoxin nonresponder mice and was also capable of stimulating IL-6 release from human monocytes. On gel chromatography, MDHM had an apparent molecular size of 1.5 x 106 daltons. Treatment with RNase and DNase had no effect on either size or biological activity. Proteinase K did not abolish activity but reduced the apparent molecular size of MDHM. MDHM production by M. fermentans required either coculture with eucaryotic cell lines in RPMI 1640 medium with fetal calf serum or addition of eucaryotic cell sonic extracts to this medium. The biological activity of MDHM is not identical to that of a mitogen for murine spleen cells derived from M. arthritidis; MDHM caused only slight proliferation in this system compared with the mitogen from M. arthritidis, and the latter did not elicit IL-6 release from macrophages. The results are discussed in relation to mycoplasmas as putative etiological agents for rheumatoid arthritis, since high IL-6 titers were reported for synovial fluid from patients with this disease.

Induction of Cytokines and Chemokines in Human Monocytes byMycoplasma fermentans-Derived Lipoprotein MALP-2

“…Our results are in line with several recent publications reporting the upregulation of TNF-␣, IL-1␤, and IL-6 expression after stimulation of monocytes with mycoplasma-derived membrane fractions (16,22,25). Gamma interferon pretreatment of murine peritoneal macrophages was reported to induce large amounts of nitric oxide when the cells were subsequently stimulated with a mycoplasma-derived high-molecular-weightmaterial (MDHM) (22).…”

Mycoplasma arginini TUH-14 membrane lipoproteins induce production of interleukin-1, interleukin-6, and tumor necrosis factor alpha by human monocytes

“…Human monocytes can be triggered by a soluble entity, isolated from Mycoplasma arthritidis culture supernatant (4), that has been shown to be a basic protein of 20 to 25 kDa (15). Mycoplasma fermentans-derived high-molecular-weight material with a molecular mass of over 1.5 x 106 Da induces IL-6 production by human monocytes; this activity requires previous culture of mycoplasma with eucaryotic cells or extracts (19). Partial biochemical characterization of the molecular moiety of TUH-14 responsible for cytokine induction showed that it consists of five membrane-bound aryl lipoproteins with molecular masses of between 60 kDa and 80 kDa (23).…”

The importance of B‐cells and ecto‐5′nucleotidase in Mycoplasma fermentans infection and the relevance to rheumatoid arthritis

“…38,39 M. fermentans has also been reported to induce a number of cytokines, such as interleukin-1 (IL-1), IL-6, granulocyte colony-stimulating factor, prostaglandins and tumour necrosis factor (TNF). [40][41][42] Christensen et al 43 reported that lymphotoxin, prostaglandin E 2 (PGE 2 ) and (in some people only) TNF would increase the 5 0 N activity of lymphocytes. The most effective was PGE 2 , which gave a threefold increase at the highest concentrations used (3 lM), whereas IL-6 had no effect.…”