A novel granulocyte-derived peptide with lipopolysaccharide-neutralizing activity.
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.
Larrick
J W
JW
Palo Alto Institute of Molecular Medicine, Mountain View, CA 94043.
Hirata
M
M
Zheng
H
H
Zhong
J
J
Bolin
D
D
Cavaillon
J M
JM
Warren
H S
HS
Wright
S C
SC
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D054804:Cathelicidins; D002460:Cell Line; D016207:Cytokines / Q000097:blood; D006098:Granulocytes / Q000737:chemistry*; D006801:Humans; D008033:Limulus Test; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D051379:Mice; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D011817:Rabbits
D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054804:Cathelicidins; D016207:Cytokines; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D009584:Nitrogen