抗菌ペプチドLL-37による好中球細胞外小胞 (エクトソーム) の放出を介したマウス敗血症の病態改善

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  • Antimicrobial peptide LL-37 ameliorates murine sepsis through the induction of microvesicle (ectosome) release from neutrophils

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<p> Neutrophils release microvesicles (ectosomes) upon stimulation. Interestingly, ectosome level is elevated in sepsis survivors. Previously, we revealed that LL-37, a human cathelicidin antimicrobial peptide, improves the survival of a murine cecal ligation and puncture (CLP) sepsis model. Thus, in the present study, we elucidated the action of LL-37 on sepsis, by focusing on the effect of LL-37 on ectosome release in the CLP model. The results demonstrated that the ectosome level was elevated in CLP mice, and the level was further enhanced by the LL-37-administration, accompanied with the reduced bacterial load. Importantly, ectosome-containing microvesicles isolated from LL-37-injected CLP mice contained higher amounts of antimicrobial proteins/peptides (such as lactoferrin and murine cathelicidin-related antimicrobial peptide), and exhibited higher antibacterial activity, compared with those from PBS-injected CLP mice, suggesting that LL-37 induces the release of ectosomes with antibacterial potential in vivo. In fact, LL-37 stimulated mouse bone marrow neutrophils to release ectosomes ex vivo, and the LL-37-induced ectosomes possessed the antibacterial activity. Furthermore, the administration of LL-37-induced ectosomes reduced the bacterial load and improved the survival of CLP mice. Together these observations suggest that LL-37 induces the release of ectosome-containing antimicrobial microvesicles in CLP mice, thereby reducing the bacterial load and protecting mice from lethal septic condition.</p>

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