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Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein
J W Larrick1, M Hirata, R F Balint
1Palo Alto Institute of Molecular Medicine, Mountain View, California 94043.
Infection and Immunity
|April 1, 1995
Summary
Researchers cloned human CAP18 and found its C-terminal fragment effectively binds lipopolysaccharide (LPS). This fragment inhibits LPS activity and protects against LPS-induced lethality, suggesting therapeutic potential.
Area of Science:
- Immunology
- Biochemistry
- Antimicrobial Research
Background:
- Human CAP18 (18-kDa cationic antimicrobial protein) is identified and purified from rabbit leukocytes.
- It binds and inhibits lipopolysaccharide (LPS) activities.
Purpose of the Study:
- To clone human CAP18 and characterize the anti-LPS activity of its C-terminal fragment.
- To investigate the therapeutic potential of human CAP18 fragments in LPS-related conditions.
Main Methods:
- Human CAP18 cDNA was identified from a bone marrow library using probes from rabbit CAP18 cDNA.
- Human CAP18 expression in granulocytes was confirmed via Western blots using specific antiserum.
- Synthetic CAP18 C-terminal fragments (CAP18(104-140) and CAP18(104-135)) were tested for LPS binding and inhibitory activities.
Main Results:
- Human CAP18 encodes a protein with a signal peptide, an N-terminal domain, and a C-terminal LPS-binding domain (CAP18(104-140)).
- The C-terminal fragments bound to LPS-coated erythrocytes and inhibited LPS-induced nitric oxide release and tissue factor generation.
- These fragments protected mice from lethal LPS challenge.
Conclusions:
- The C-terminal fragment of human CAP18 exhibits potent anti-LPS activity.
- Human CAP18 is specifically expressed in granulocytes.
- CAP18(104-140) demonstrates therapeutic potential for treating LPS-associated conditions.