MDHM, a macrophage-activating product ofMycoplasma fermentans, stimulates murine macrophages to synthesize nitric oxide and become tumoricidal

Abstract

In continuation of previous work on macrophage activation by a Mycoplasma fermentans-derived product, originally named "mycoplasma-derived high mol. wt. material" (MDHM), we have investigated whether MDHM was capable of inducing synthesis of the reactive nitrogen intermediate nitric oxide (NO), thus rendering macrophages cytocidal. Mycoplasmas were first delipidated with acetone, and MDHM activity was then extracted with 50 mM 1-O-octyl-beta-D-glucopyranoside to yield a particularly active new preparation of MDHM which we have named MDHM-D (D for detergent). In combination with IFN-gamma, MDHM-D activated macrophages to produce reactive nitrogen intermediates and kill P815 mastocytoma cells in co-culture. P815 target cells were chosen because they are TNF-resistant. Macrophages from the LPS-low responder strain C3H/HeJ were used to minimize interference from possible LPS contamination. MDHM-D activity in this system was strictly IFN-gamma-dependent. In the presence of 25 U/ml IFN-gamma MDHM-D gave a half maximal response at a dilution of 1/100,000, showing a parallel concentration dependency for nitrite production and cytocidal activity.

Stimulation of pulmonary immune responses by the TLR2/6 agonist MALP‐2 and effect on melanoma metastasis to the lung

“…Some macrophages can kill tumor cells by antibody‐dependent or antibody‐independent mechanisms (50,51). Of note, particularly, TLR‐activated macrophages may possess direct tumoricidal activity (15), and TLR agonists can arm macrophages against tumor cells (14,30,52). Moreover, MALP‐2 may help to link innate and adaptive immune responses against cancer cells through activation of dendritic cells (31,34).…”

“…Macrophages are thus stimulated to produce proinflammatory cytokines and chemokines including TNFα, IL‐6, IL‐8, GROα, MCP‐1, MIP‐1α and MIP‐1β (27,28). The net result is immigration of different leucocytes, immune stimulation (28,29) and increased tumoricidal activity of macrophages in vitro (30). In addition, MALP‐2 induces dendritic cell maturation and, therefore, is involved in the communication between innate and adaptive immunity (31–34).…”

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