Effects of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) pretreatment on septic rats.
To evaluate the effects of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) injection on the survival rate of rats post cecal ligation and puncture (CLP), Sprague-Dawley (SD) rats were subcutaneously injected with 0.125 ml, 0.25 ml or 0.5 ml PA-MSHA for 8 days or 16 days before CLP. The survival rate and physiological appearance of rats in each group were monitored daily post CLP. The expression of Toll-like receptor 4 (TLR4) and cytokines related to inflammation was evaluated. We found that the 0.5 ml-8d (0.5 ml PA-MSHA injected for 8 days) group had the highest 7-day survival rate (91.7%), which was significantly improved compared with the CLP-only group (33.3%). Furthermore, our results showed that PA-MSHA effectively increased serum pro-inflammatory mediators (TNF-α, IL-1β and IL-6) at the early stage (8 days) but increased anti-inflammatory mediators (IL-4 and IL-10) at the late stage (16 days). PA-MSHA significantly up-regulated the mRNA expression of TLR4 at 8 and 16 days. After PA-MSHA pretreatment, CLP had no marked effect on the levels of most inflammatory factors. To explore potential protective mechanisms of PA-MSHA against CLP, we examined the effect of PA-MSHA on murine macrophage-like RAW264.7 cells and found that PA-MSHA induced endotoxin tolerance. In conclusion, this study suggested that precisely controlling the dosage and time of PA-MSHA administration can effectively increase the rat survival rate post CLP, which may be mediated through regulating inflammatory mediators and inducing endotoxin tolerance.
Department of Critical Care Medicine, Huashan Hospital, Fudan University, China. Electronic address: drzhuhechen@126.com.
Hechen
H
Zhu
Shiqiang
S
Wang
Lei
L
Shen
Wei
W
Wang
Feng
F
Zhao
Tongwa
T
Cao
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000097:blood; D006388:Hemagglutinins / Q000494:pharmacology*; D007108:Immune Tolerance; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008297:Male; D008358:Mannose / Q000494:pharmacology*; D051379:Mice; D011550:Pseudomonas aeruginosa; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D006388:Hemagglutinins; D008070:Lipopolysaccharides; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D008358:Mannose
Cecal ligation and puncture (CLP); Cytokines; Endotoxin tolerance; Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA); Sepsis; Toll-like receptor 4