Antimicrobial peptide LL-37 ameliorates a murine sepsis model via the induction of microvesicle release from neutrophils
Autor: | Toshiaki Iba, Taisuke Murakami, Isao Nagaoka, Johannes Reich, Kuwahara-Arai, Yumi Kumagai |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy ectosome Neutrophils Immunology Peptide Microbiology Neutrophil Activation Sepsis 03 medical and health sciences Mice 0302 clinical medicine antibacterial activity In vivo Cell-Derived Microparticles Cathelicidins medicine Animals Humans Molecular Biology Cecum Cells Cultured chemistry.chemical_classification Mice Inbred BALB C antimicrobial peptide LL-37 Microvesicle neutrophil Cell Biology Original Articles Antimicrobial medicine.disease Microvesicles Bacterial Load Disease Models Animal 030104 developmental biology Infectious Diseases chemistry 030220 oncology & carcinogenesis Female Antibacterial activity lcsh:RC581-607 Ex vivo Antimicrobial Cationic Peptides |
Zdroj: | Innate Immunity Innate Immunity, Vol 26 (2020) |
ISSN: | 1753-4267 |
Popis: | Sepsis is a life-threatening disease caused by systemic dys-regulated inflammatory response to infection. We previously revealed that LL-37, a human cathelicidin antimicrobial peptide, improves the survival of cecal ligation and puncture septic mice. Ectosomes, microvesicles released from neutrophils, are reported to be elevated in sepsis survivors; however, the functions of ectosomes in sepsis remain largely unknown. Therefore, we herein elucidated the protective action of LL-37 on sepsis, by focusing on LL-37-induced ectosome release in a cecal ligation and puncture model. The results demonstrated the enhancement of ectosome levels by LL-37 administration, accompanied by a reduction of bacterial load. Importantly, ectosomes isolated from LL-37-injected cecal ligation and puncture mice contained higher amounts of antimicrobial proteins/peptides and exhibited higher antibacterial activity, compared with those from PBS-injected cecal ligation and puncture mice, suggesting that LL-37 induces the release of ectosomes with antibacterial potential in vivo. Actually, LL-37 stimulated mouse bone-marrow neutrophils to release ectosomes ex vivo, and the LL-37-induced ectosomes possessed antibacterial potential. Furthermore, administration of LL-37-induced ectosomes reduced the bacterial load and improved the survival of cecal ligation and puncture mice. Together these observations suggest LL-37 induces the release of antimicrobial ectosomes in cecal ligation and puncture mice, thereby reducing the bacterial load and protecting mice from lethal septic conditions. |
Databáze: | OpenAIRE |
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