MALP-2, a Mycoplasma lipopeptide with classical endotoxic properties: end of an era of LPS monopoly?
Although some activities of LPS are shared by other bacterial components, for half a century LPS has been regarded as unique in displaying many pathophysiological activities. Here we report on a synthetic lipopeptide, MALP-2 from Mycoplasma fermentans, which expresses potent endotoxin-like activity and whose lethal toxicity is comparable to that of LPS. With the exception of the Limulus lysate gelation test, in which MALP-2 was approximately 1000-fold less active than LPS, the synthetic lipopeptide induced all activities tested for, and in most cases to an extent comparable to that of LPS. Unlike LPS, the biological activities of MALP-2 were expressed both in LPS-responder and in LPS-non-responder mice (BALB/c/l, C57BL10/ScCr), indicating that MALP-2 signaling, unlike that of LPS, is not transduced via the Toll-like receptor (Tlr) 4 protein.MALP-2 expressed no toxicity in normal or sensitized Tlr2 knockout (Tlr2(-/-)) mice indicating that its toxic activity is induced via Tlr2 signaling. The phenomenology of the lethal shock induced by MALP-2 in normal or sensitized mice, i.e. the kinetics of its development and symptoms of illness exhibited by the treated animals, was very reminiscent of the lethal shock induced by LPS.
Galanos
C
C
Max-Planck Institut für Immunbiologie, Freiburg, Germany.
Gumenscheimer
M
M
Mühlradt
P
P
Jirillo
E
E
Freudenberg
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D029721:Drosophila Proteins; D004351:Drug Resistance; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000633:toxicity; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D016858:Mycoplasma fermentans / Q000472:pathogenicity*; D009336:Necrosis; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology / Q000633:toxicity*; D011425:Propionibacterium acnes / Q000276:immunology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D017471:Receptors, Interferon / Q000235:genetics / Q000502:physiology; D012772:Shock, Septic / Q000209:etiology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000096743:Interferon gamma Receptor
D016207:Cytokines; D029721:Drosophila Proteins; D004731:Endotoxins; D055666:Lipopeptides; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008934:Mitogens; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D017471:Receptors, Interferon; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000096743:Interferon gamma Receptor; C106335:macrophage stimulatory lipopeptide 2