The human antibacterial cathelicidin, hCAP-18, is bound to lipoproteins inplasma

Cathelicidins are a family of antibacterial and lipopolysaccharide-binding proteins. hCAP-18, the only human cathelicidin, is a major protein of the s pecific granules of human neutrophils, The plasma level of hCAP-18 is >20-f old higher than that of other specific granule proteins relative to their l evels within circulating neutrophils, The aim of this study was to elucidat e the background for this high plasma level of hCAP-18. Plasma was subjecte d to molecular sieve chromatography, and hCAP-18 was found in distinct high molecular mass fractions that coeluted with apolipoproteins A-I and B, res pectively. The association of hCAP-18 with lipoproteins was validated by th e cofractionation of hCAP-18 with lipoproteins using two different methods for isolation of lipoproteins from plasma. Furthermore, the level of hCAP-1 8 in delipidated plasma was <1% of that in normal plasma. Immunoprecipitati on of very low, low, and high density lipoprotein particles with anti-apoli poprotein 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 lipopr oteins may play an important role as a reservoir of this antimicrobial prot ein.