The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils
(1997) In Blood 90(7). p.803-2796- 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... (More)
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.
(Less)
- author
- Sørensen, O LU ; Arnljots, K LU ; Cowland, J B ; Bainton, D F and Borregaard, N
- publishing date
- 1997
- type
- Contribution to journal
- publication status
- published
- keywords
- Antimicrobial Cationic Peptides, Bone Marrow Cells, Carrier Proteins, Cathelicidins, Cell Differentiation, Cytoplasmic Granules, Enzyme Precursors, Exocytosis, Gelatinases, Hematopoietic Stem Cells, Humans, Ionomycin, Lactoferrin, Microscopy, Immunoelectron, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils, Peroxidase, Subcellular Fractions, Journal Article
- in
- Blood
- volume
- 90
- issue
- 7
- pages
- 803 - 2796
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:9326247
- scopus:0030880531
- ISSN
- 0006-4971
- language
- English
- LU publication?
- no
- id
- 1d109df9-c0c7-4ccf-a04a-8762e6cf8d1b
- date added to LUP
- 2018-03-07 10:02:52
- date last changed
- 2024-06-11 11:52:41
@article{1d109df9-c0c7-4ccf-a04a-8762e6cf8d1b,
abstract = {{<p>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.</p>}},
author = {{Sørensen, O and Arnljots, K and Cowland, J B and Bainton, D F and Borregaard, N}},
issn = {{0006-4971}},
keywords = {{Antimicrobial Cationic Peptides; Bone Marrow Cells; Carrier Proteins; Cathelicidins; Cell Differentiation; Cytoplasmic Granules; Enzyme Precursors; Exocytosis; Gelatinases; Hematopoietic Stem Cells; Humans; Ionomycin; Lactoferrin; Microscopy, Immunoelectron; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Peroxidase; Subcellular Fractions; Journal Article}},
language = {{eng}},
number = {{7}},
pages = {{803--2796}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils}},
volume = {{90}},
year = {{1997}},
}