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Structure and functions of endotoxin-binding peptides derived from CAP18
M Hirata1, J Zhong, S C Wright
1Department of Bacteriology, School of Medicine, Iwate Medical University, Morioka, Japan.
Progress in Clinical and Biological Research
|January 1, 1995
Summary
Cationic antimicrobial protein 18 (CAP18) and its C-terminal peptides bind to lipopolysaccharide (LPS), neutralizing its effects and protecting against endotoxin shock. These peptides also exhibit broad antimicrobial activity, suggesting therapeutic potential for infectious diseases.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- CAP18 is a cationic antimicrobial protein found in rabbit and human granulocytes.
- It comprises an N-terminal domain and a C-terminal LPS-binding domain.
- LPS is a key component of Gram-negative bacteria that triggers inflammatory responses.
Purpose of the Study:
- To investigate the LPS-binding and neutralizing activities of CAP18 C-terminal fragments.
- To evaluate the antimicrobial properties of these peptides.
- To assess the therapeutic potential of CAP18-derived peptides in models of LPS-induced toxicity and infection.
Main Methods:
- Synthesis and characterization of CAP18 C-terminal peptides.
- Assays for LPS-binding, inhibition of LPS-induced cytokine production (TNF), tissue factor generation, and nitric oxide release.
- In vivo studies using mouse models of LPS lethality.
- Antimicrobial activity testing against Gram-negative and Gram-positive bacteria.
Main Results:
- Synthetic peptides CAP18106-142 and CAP18106-137 effectively bound LPS and inhibited LPS-induced inflammatory responses.
- These peptides protected mice from lethal endotoxemia.
- Broad-spectrum antimicrobial activity was observed against both Gram-negative (E. coli, S. typhimurium) and Gram-positive (S. aureus, S. pneumoniae) bacteria.
- Human CAP18 showed high homology to rabbit CAP18, and its C-terminal fragment also demonstrated LPS-neutralizing and antimicrobial properties.
Conclusions:
- CAP18 C-terminal peptides are potent LPS-binding and neutralizing agents.
- These peptides possess significant antimicrobial activity and protective effects against endotoxemia.
- CAP18 and its derivatives represent promising candidates for therapeutic intervention in sepsis and other infectious diseases.