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Updated: Apr 14, 2026
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Lipopolysaccharide-binding protein (LBP) blockade augments the protective effect of granulocyte colony-stimulating
Anding Liu1, Stefanie Weiss, Haoshu Fang
1*Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; †Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany; ‡Department of Pathophysiology, Anhui Medical University, Hefei, China; §Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany; ∥Institute of Medical Microbiology, Jena University Hospital, Jena, Germany; and ¶Institute for Pathology, Jena University Hospital, Jena, Germany.
Abstract:
The effect of granulocyte colony-stimulating factor (G-CSF) on sepsis is discussed controversially in clinical studies. We previously demonstrated that G-CSF treatment induced lipopolysaccharide (LPS) sensitization via up-regulation of LPS-binding protein (LBP). We hypothesized that the futile effect of G-CSF-treatment in sepsis might be due to its ability to up-regulate LBP. Therefore, blockade of LBP may attenuate the G-CSF-induced LPS sensitization and protect animals from polymicrobial sepsis. Endogenous LBP levels were up-regulated by pretreatment with G-CSF, and the LBP protein was blocked by administration of a specific blocking peptide-LBPK95A. Polymicrobial sepsis was induced by intraperitoneal injection of feces slurry. Rats were monitored every 3 up to 72 h to observe the survival rate. Tissue injury, bacterial infiltration, local inflammatory response, and neutrophil infiltration at 0, 2, and 12 h after the septic insult were analyzed. The survival benefit of G-CSF pretreatment was improved when combined with LBPK95A treatment (control vs. G-CSF vs. combi: 36% vs. 56% vs. 93%; P < 0.05). Combined treatment of G-CSF and LBPK95A was associated with the minimal tissue damage. Treatment with LBPK95A significantly inhibited the neutrophil infiltration without interfering with the bacterial clearance. The G-CSF-induced inflammatory sensitization effect was inhibited by LBPK95A, indicated by the decrease of cytokines expression, and the activation of nuclear factor kappa B and signal transducer and activator of transcription 3 signaling pathway. In conclusion, these results suggested that the effect of prophylactic augmentation of the host's response via G-CSF pretreatment was further enhanced by inhibition of the up-regulation of LBP.
