Advanced

The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils

Sørensen, O LU ; Arnljots, K LU ; Cowland, J B; Bainton, D F and Borregaard, N (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)
Please use this url to cite or link to this publication:
author
publishing date
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
  • 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
2018-11-11 05:00:45
@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},
  keyword      = {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},
}