Involvement of Small GTPases in Mycoplasma fermentans Membrane Lipoproteins-mediated Activation of Macrophages

• Published in: The Journal of biological chemistry Vol. 274; no. 43; pp. 30794 - 30798
• Main Authors: Rawadi, Georges, Zugaza, Jose-Luis, Lemercier, Brigitte, Marvaud, Jean Christophe, Popoff, Michel, Bertoglio, Jacques, Roman-Roman, Sergio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22-10-1999
• Subjects: Animals; Bacterial Toxins - toxicity; cdc42 GTP-Binding Protein - metabolism; Cell Line; Cell Membrane - physiology; GTP Phosphohydrolases - metabolism; GTPase-Activating Proteins - metabolism; Lipoproteins - pharmacology; Macrophage Activation - physiology; Macrophages - physiology; Mycoplasma fermentans; Mycoplasma fermentans - physiology; rac GTP-Binding Proteins - metabolism; Recombinant Fusion Proteins - metabolism; Transfection; Tumor Necrosis Factor-alpha - biosynthesis; Virulence Factors, Bordetella - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.43.30794

Mycoplasma fermentans lipoproteins (LAMPf) are capable of activating macrophages and inducing the secretion of proinflammatory cytokines. We have recently reported that mitogen-activated protein kinase (MAPK) pathways and NF-κB and activated protein 1 (AP-1) play a crucial role in the activation induced by this bacterial compound. To further elucidate the mechanisms by which LAMPf mediate the activation of macrophages, we assessed the effects of inhibiting small G proteins Rac, Cdc42, and Rho. The Rho-specific inhibitor C3 enzyme completely abolished the secretion of tumor necrosis factor α by macrophages stimulated with LAMPf and also inhibited the activation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 kinase. In addition, we have shown that LAMPf stimulate Cdc42 and that inhibition of Cdc42 or Rac by dominant negative mutants abrogates LAMPf-mediated activation of JNK and transactivation of NF-κB and AP-1 in the murine macrophage cell line RAW 264.7. These results indicate that small G proteins Rho, Cdc42, and Rac are involved in the cascade of events leading to the macrophage activation by mycoplasma lipoproteins.