Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3
(2001) In Blood 97(12). p.3951-3959- Abstract
- Cathelicidins are a family of antimicrobial proteins found in the peroxidase-negative granules of neutrophils. The known biologic functions reside in the C-terminus, which must be cleaved from the holoprotein to become active. Bovine and porcine cathelicidins are cleaved by elastase from the azurophil granules to yield the active antimicrobial peptides. The aim of this study was to identify the physiological setting for cleavage of the only human cathelicidin, hCAP-18, to liberate the antibacterial and cytotoxic peptide LL-37 and to identify the protease responsible for this cleavage. Immunoelectron microscopy demonstrated that both hCAP-18 and azurophil granule proteins were present in the phagolysosome. Immunoblotting revealed no... (More)
- Cathelicidins are a family of antimicrobial proteins found in the peroxidase-negative granules of neutrophils. The known biologic functions reside in the C-terminus, which must be cleaved from the holoprotein to become active. Bovine and porcine cathelicidins are cleaved by elastase from the azurophil granules to yield the active antimicrobial peptides. The aim of this study was to identify the physiological setting for cleavage of the only human cathelicidin, hCAP-18, to liberate the antibacterial and cytotoxic peptide LL-37 and to identify the protease responsible for this cleavage. Immunoelectron microscopy demonstrated that both hCAP-18 and azurophil granule proteins were present in the phagolysosome. Immunoblotting revealed no detectable cleavage of hCAP-18 in cells after phagocytosis. In contrast, hCAP-18 was cleaved to generate LL-37 in exocytosed material. Of the 3 known serine proteases from azurophil granules, proteinase 3 was solely responsible for cleavage of hCAP-18 after exocytosis. This is the first detailed study describing the generation of a human antimicrobial peptide from a promicrobicidal protein, and it demonstrates that the generation of active antimicrobial peptides from common proproteins occurs differently in related species. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1119950
- author
- Sørensen, Ole E LU ; Follin, Per ; Johnsen, Anders H. ; Calafat, Jero ; Tjabringa, G. Sandra ; Hiemstra, Pieter S. and Borregaard, Niels
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 97
- issue
- 12
- pages
- 3951 - 3959
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:11389039
- scopus:0035877995
- ISSN
- 1528-0020
- DOI
- 10.1182/blood.V97.12.3951
- language
- English
- LU publication?
- yes
- id
- 17330cc5-eb03-425b-b1b7-17b107f16992 (old id 1119950)
- date added to LUP
- 2016-04-01 12:26:49
- date last changed
- 2025-04-04 15:13:57
@article{17330cc5-eb03-425b-b1b7-17b107f16992,
abstract = {{Cathelicidins are a family of antimicrobial proteins found in the peroxidase-negative granules of neutrophils. The known biologic functions reside in the C-terminus, which must be cleaved from the holoprotein to become active. Bovine and porcine cathelicidins are cleaved by elastase from the azurophil granules to yield the active antimicrobial peptides. The aim of this study was to identify the physiological setting for cleavage of the only human cathelicidin, hCAP-18, to liberate the antibacterial and cytotoxic peptide LL-37 and to identify the protease responsible for this cleavage. Immunoelectron microscopy demonstrated that both hCAP-18 and azurophil granule proteins were present in the phagolysosome. Immunoblotting revealed no detectable cleavage of hCAP-18 in cells after phagocytosis. In contrast, hCAP-18 was cleaved to generate LL-37 in exocytosed material. Of the 3 known serine proteases from azurophil granules, proteinase 3 was solely responsible for cleavage of hCAP-18 after exocytosis. This is the first detailed study describing the generation of a human antimicrobial peptide from a promicrobicidal protein, and it demonstrates that the generation of active antimicrobial peptides from common proproteins occurs differently in related species.}},
author = {{Sørensen, Ole E and Follin, Per and Johnsen, Anders H. and Calafat, Jero and Tjabringa, G. Sandra and Hiemstra, Pieter S. and Borregaard, Niels}},
issn = {{1528-0020}},
language = {{eng}},
number = {{12}},
pages = {{3951--3959}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3}},
url = {{http://dx.doi.org/10.1182/blood.V97.12.3951}},
doi = {{10.1182/blood.V97.12.3951}},
volume = {{97}},
year = {{2001}},
}