Prevention of death in bacterium-infected mice by a synthetic antimicrobial peptide, L5, through activation of host immunity.
In our previous study, we found that the antibacterial peptide KLKLLLLLKLK-NH(2) (L5) and its d-enantiomer (DL5) activate neutrophils to produce superoxide anions (O(2)(-)) and prevent death due to infection by methicillin-resistant Staphylococcus aureus, suggesting that these peptides may elicit in vivo antimicrobial activities through host inflammatory responses mediated by neutrophils. In this study, we investigated the mechanisms behind in vivo antimicrobial prophylaxis by the use of L5 for the treatment of bacterial infection introduced via intra-abdominal implantation. We found that the intraperitoneal treatment with L5 before bacterial infection markedly reduced rates of death due to infection. Treatments with L5 were highly effective in preventing death due to intraperitoneal inoculation of not only S. aureus Smith but also Enterococcus faecalis SR1004 and Escherichia coli EC14. The intra-abdominal administration of L5 induced accumulation of neutrophils, increased levels of reactive oxygen species, and augmented antibacterial activity in the abdominal cavity. In addition, administration of L5 upregulated the expression of the Mig/CXCL9 chemokine gene in thioglycolate-elicited peritoneal macrophages. Our results suggested that the prevention of death by treatment of infected mice with L5 might occur primarily through the activation of a host immune response.
Okuyama-Nishida
Yukiko
Y
Natori Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Akiyama
Nobuko
N
Sugimori
Giichi
G
Nomura
Kazuhide
K
Ogawa
Kenji
K
Homma
Koichi J
KJ
Sekimizu
Kazuhisa
K
Tsujimoto
Masafumi
M
Natori
Shunji
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000276:immunology* / Q000401:mortality; D054370:Chemokine CXCL9 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D018375:Neutrophil Activation / Q000187:drug effects*; D009842:Oligopeptides / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D054370:Chemokine CXCL9; C485969:Cxcl9 protein, mouse; D009842:Oligopeptides; D017382:Reactive Oxygen Species