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The Journal of Immunology, Vol 152, Issue 1 231-240, Copyright © 1994 by American Association of Immunologists

ARTICLES

A novel granulocyte-derived peptide with lipopolysaccharide- neutralizing activity

JW Larrick, M Hirata, H Zheng, J Zhong, D Bolin, JM Cavaillon, HS Warren and SC Wright
Palo Alto Institute of Molecular Medicine, Mountain View, CA 94043.

Rabbit CAP18 (cationic antimicrobial protein, 18 kDa) is a leukocyte protein identified and purified using as an assay its capacity to bind and inhibit various activities of LPS. Oligonucleotide probes designed from the putative N-terminal protein sequence were used to obtain the corresponding cDNA from a rabbit bone marrow cDNA library. Examination of the cDNA sequence revealed that the protein fragment of the putative N-terminus was actually a 37-amino-acid C-terminal fragment. This fragment, designated CAP18(106-142), inhibits many activities of LPS. In the present studies, synthetic CAP18(106-142) is shown to: 1) bind to erythrocytes coated with diverse strains of LPS; 2) inhibit LPS- induced release of cytokines (TNF, IL-1, IL-6) and nitric oxide from macrophages; 3) inhibit LPS-induced LAL coagulation and 4) protect mice from LPS lethality. CAP18(106-142) may have therapeutic utility for conditions associated with elevated concentrations of LPS.


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