The Human Antibacterial Cathelicidin, hCAP-18, Is Synthesized in Myelocytes and Metamyelocytes and Localized to Specific Granules in Neutrophils

Abstract

hCAP-18 is the only human member of the antibacterial and endotoxin-binding 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 neutralizing N-terminus by proteases from peroxidase positive granules. In human neutrophils, peroxidase positive and peroxidase negative granules can be subdivided into granule subsets that differ in protein content and ability to be exocytosed. To determine the localization of hCAP-18, we performed high-resolution immuno-electron microscopy and subcellular fractionation on Percoll density gradients. Biosynthesis of hCAP-18 was investigated in isolated human bone marrow cells. hCAP-18 was found to colocalize and comobilize with lactoferrin, but not with gelatinase in subcellular fractions. This was confirmed by electron microscopy. hCAP-18 is synthesized at the same stage of myeloid cell maturation 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.

Association of vitamin D and antimicrobial peptide production during late‐phase allergic responses in the lung

“…CAMP, also known as hCAP 18; or its cleaved, antimicrobial, 37 amino acid residue, LL‐37; is the only human cathelicidin . The majority of CAMP is found in neutrophil granules , but is also expressed in other inflammatory cells including natural killer cells, γδ T cells, B cells, monocytes, and mast cells . High levels are present in plasma , and vitamin D supplementation can increase circulating levels .…”

“…One of the most prominent genes up‐regulated by 1,25(OH) 2 D is human cathelicidin antimicrobial peptide (CAMP) , a major component of the innate immune response to infectious agents with broad antimicrobial activities. Cathelicidin is found in the secondary granules of neutrophils and other leucocytes ; in barrier epithelial cells, including skin, mouth, intestine, and the airway ; and in plasma at high levels .…”

Cathelicidin is involved in the intracellular killing of mycobacteria in macrophages

“…Two main families of AMPs in mammals, the defensins and the cathelicidins, are expressed in different cells such as neutrophils, macrophages, monocytes, myeloid bone marrow cells and epithelial cells. In contrast to the multiple defensins, only one cathelicidin gene, CAMP , has been found in humans (Sorensen et al ., 1997a; Agerberth et al ., 2000). The gene product human cationic antimicrobial peptide‐18 (hCAP18) is synthesized as a propeptide that is then cleaved extracellularly into cathelin and the C‐terminal LL‐37, the latter exhibiting a broad antimicrobial activity (Sorensen et al ., 2001).…”

Topical treatment with the vitamin D analogue calcipotriol enhances the upregulation of the antimicrobial protein hCAP18/LL‐37 during wounding in human skin in vivo

“…hCAP18/LL‐37 is produced in leukocytes and is widely expressed in squamous epithelia of the skin and the airways, in the gastrointestinal and genital tracts (12–16) as well as in exocrine and apocrine glands and their secretions (17–21). In normal intact skin there is low constitutive expression of hCAP18 but upon inflammation there is strong upregulation (15,22).…”