title: The human antibacterial cathelicidin, hCAP-18, is bound to lipoproteins in plasma.
abstract: Cathelicidins are a family of antibacterial and lipopolysaccharide-binding proteins. hCAP-18, the only human cathelicidin, is a major protein of the specific granules of human neutrophils. The plasma level of hCAP-18 is >20-fold higher than that of other specific granule proteins relative to their levels within circulating neutrophils. The aim of this study was to elucidate the background for this high plasma level of hCAP-18. Plasma was subjected to molecular sieve chromatography, and hCAP-18 was found in distinct high molecular mass fractions that coeluted with apolipoproteins A-I and B, respectively. The association of hCAP-18 with lipoproteins was validated by the cofractionation of hCAP-18 with lipoproteins using two different methods for isolation of lipoproteins from plasma. Furthermore, the level of hCAP-18 in delipidated plasma was <1% of that in normal plasma. Immunoprecipitation of very low, low, and high density lipoprotein particles with anti-apolipoprotein antibodies resulted in coprecipitation of hCAP-18. The binding of hCAP-18 to lipoproteins was mediated by the antibacterial C-terminal part of the protein. The binding of hCAP-18 to lipoproteins suggests that lipoproteins may play an important role as a reservoir of this antimicrobial protein.
authors.affiliation: Granulocyte Research Laboratory, Department of Hematology, the Finsen Centre, National University Hospital, DK-2100 Copenhagen O, Denmark. olesoren@rh.dk
authors.forename: O
authors.initials: O
authors.lastname: Sørensen
authors.forename: T
authors.initials: T
authors.lastname: Bratt
authors.forename: A H
authors.initials: AH
authors.lastname: Johnsen
authors.forename: M T
authors.initials: MT
authors.lastname: Madsen
authors.forename: N
authors.initials: N
authors.lastname: Borregaard
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000302:isolation & purification* / Q000378:metabolism; D001665:Binding Sites; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000302:isolation & purification* / Q000378:metabolism; D002352:Carrier Proteins / Q000302:isolation & purification* / Q000378:metabolism; D054804:Cathelicidins; D005089:Exocytosis; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000737:chemistry; D008079:Lipoproteins, VLDL / Q000737:chemistry; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000737:chemistry; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000302:isolation & purification
chemical_list: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D054804:Cathelicidins; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; C084515:cathelin