2010
DOI: 10.1097/shk.0b013e3181cdc50f
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M1 Protein From Streptococcus Pyogenes Induces Nitric Oxide-Mediated Vascular Hyporesponsiveness to Phenylephrine

Abstract: Streptococcus pyogenes carrying M1 protein causes the severe and increasingly prevalent streptococcal toxic shock syndrome and necrotizing fasciitis. M1 protein is an important virulence factor of S. pyogenes and induces an inflammatory response in human monocytes. We wanted to investigate if purified M1 protein in solution could induce vascular NO production leading to vasopressor hyporesponsiveness. Rat aortic segments were incubated with M1 protein or LPS in vitro. M1 protein (10 microg mL) and LPS (1 ng mL… Show more

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Cited by 11 publications
(8 citation statements)
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“…The substantial hyaluronic acid capsule or its degradation products are known to induce TLR2- and TLR4-mediated inflammation [27], [28], and TLR2 agonists are known to promote Th17 differentiation [29]. M1 protein is also a TLR2 agonist [30] and known to induce inflammatory cytokines, including IL-6 [31] and TGF-β1 [32], and is, therefore, another potential PAMP that could direct a Th17 response. The finding that intranasal inoculation, even with heat-killed GAS-2W cells induces an antigen-specific Th17 response, while other routes induce a Th1 response also has important implications for development and delivery of vaccines to protect against GAS and other mucosal pathogens.…”
Section: Discussionmentioning
confidence: 99%
“…The substantial hyaluronic acid capsule or its degradation products are known to induce TLR2- and TLR4-mediated inflammation [27], [28], and TLR2 agonists are known to promote Th17 differentiation [29]. M1 protein is also a TLR2 agonist [30] and known to induce inflammatory cytokines, including IL-6 [31] and TGF-β1 [32], and is, therefore, another potential PAMP that could direct a Th17 response. The finding that intranasal inoculation, even with heat-killed GAS-2W cells induces an antigen-specific Th17 response, while other routes induce a Th1 response also has important implications for development and delivery of vaccines to protect against GAS and other mucosal pathogens.…”
Section: Discussionmentioning
confidence: 99%
“…Porphyromonas gingivalis fimbriae, a major virulence factor of this pathogen, are able to link CD14 and CD11b/18, following which TLRs are recruited as signal receptors (14). The M1 protein of Streptococcus pyogenes binds to TLR2 and TLR4 (54). Both the native mannosylated MP65 protein (a ␤-glucanase adhesin) and the recombinant protein (rMP65) of Candida albicans were efficiently bound and taken up by macrophages and dendritic cells in a process involving both clathrin-dependent and clathrin-independent mechanisms.…”
mentioning
confidence: 99%
“…NO is rapidly oxidized to nitrite and nitrate, and therefore levels of these substances can be used as an indicator of NO production. Nitrite/nitrate was measured as previously described [ 12 ].…”
Section: Methodsmentioning
confidence: 99%
“…M1 protein also produces a direct vascular effect. Rat and mouse aorta segments incubated with M1 protein shows a lowered constrictive response to the α-adrenoceptor agonist, phenylephrine, a vasoplegic effect mediated via an M1 protein/Toll-like receptor (TLR)4 interaction [ 12 ].…”
Section: Introductionmentioning
confidence: 99%