THE HUMAN ANTIBACTERIAL CATHELICIDIN, HCAP-18, IS SYNTHESIZED IN MYELOCYTES AND METAMYELOCYTES AND LOCALIZED TO SPECIFIC GRANULES IN NEUTROPHILS

hCAP-18 is the only human member of the antibacterial and endotoxin-bi nding family of proteins known as cathelicidins. The antibacterial and endotoxin binding domains reside in the C-terminal 37 amino acids of the protein (LL-37) and this is believed to be unleashed from the neut ralizing N-terminus by proteases from peroxidase positive granules, In human neutrophils, peroxidase positive and peroxidase negative granul es can be subdivided into granule subsets that differ in protein conte nt and ability to be exocytosed. To determine the localization of hCAP -18, we performed high-resolution immune-electron microscopy and subce llular fractionation on Percoll density gradients, Biosynthesis of hCA P-18 was investigated in isolated human bone marrow cells, hCAP-18 was found to colocalize and comobilize with lactoferrin, but not with gel atinase in subcellular fractions, This was confirmed by electron micro scopy, hCAP-18 is synthesized at the same stage of myeloid cell matura tion as lactoferrin, and is efficiently targeted to granules. Like the peroxidase negative granule's matrix metalloproteinases, collagenase and gelatinase, hCAP-18 is also stored in unprocessed form, hCAP-18 is a major protein of specific granules where it is present in equimolar ratio with lactoferrin, (C) 1997 by The American Society of Hematolog y.