Release of neutrophil proteinase 4(3) and leukocyte elastase during phagocytosis and their interaction with proteinase inhibitors
(1992) In Scandinavian Journal of Clinical and Laboratory Investigation 52(8). p.823-829- Abstract
Neutrophil proteinase 4 (NP4) is a major neutral proteinase of the human polymorphonuclear (PMN) leukocyte, which is present in amounts similar to leukocyte elastase. NP4(3) is a potent, non-specific proteinase, which may degrade structural and soluble proteins in the tissues and body fluids, and it has been implicated as an important pathogenetic factor in lung emphysema. We have studied the release of elastase and NP4(3) in an in vitro model of phagocytosis, α1-pproteinase inhibitor (α1-PI) is the major plasma inhibitor of both leukocyte elastase and NP4(3), but α1-PI bound leukocyte elastase more readily than NP4(3). The basic conditions were designed so that some proteolytic activity was present in... (More)
Neutrophil proteinase 4 (NP4) is a major neutral proteinase of the human polymorphonuclear (PMN) leukocyte, which is present in amounts similar to leukocyte elastase. NP4(3) is a potent, non-specific proteinase, which may degrade structural and soluble proteins in the tissues and body fluids, and it has been implicated as an important pathogenetic factor in lung emphysema. We have studied the release of elastase and NP4(3) in an in vitro model of phagocytosis, α1-pproteinase inhibitor (α1-PI) is the major plasma inhibitor of both leukocyte elastase and NP4(3), but α1-PI bound leukocyte elastase more readily than NP4(3). The basic conditions were designed so that some proteolytic activity was present in the medium. Addition of increasing amounts of Secretory leukocyte protease inhibitor (SLPI) to the incubation mixtures resulted in binding of leukocyte elastase to this inhibitor and extinction of free proteolytic activity against both natural and synthetic substrates. The progressive binding of leukocyte elastase to SLPI instead of α1-PI was paralleled by an increasing binding of NP4(3) to α1-PI. SLPI is a potent inhibitor of leukocyte elastase and cathepsin G, and although it lacks inhibitory effect on NP4(3), it may obviously indirectly aid in the binding and inhibition of NP4(3) to α1-PI, by taking care of at least part of the leukocyte elastase. As a specific NP4(3)-inhibitor is not readily available for therapeutic use, this effect may prove useful under in vivo conditions and enhance the protective effect of administered recombinant human SLPI.
(Less)
- author
- Bergenfeldt, M. LU ; Axelsson, L. LU and Ohlsson, K.
- organization
- publishing date
- 1992
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Leukocyte elastase, Neutrophil proteinase 4, Phagocytosis, Proteinase-3, Secretory leukocyte protease inhibitor
- in
- Scandinavian Journal of Clinical and Laboratory Investigation
- volume
- 52
- issue
- 8
- pages
- 7 pages
- publisher
- Informa Healthcare
- external identifiers
-
- scopus:0026621989
- pmid:1362620
- ISSN
- 0036-5513
- DOI
- 10.3109/00365519209088387
- language
- English
- LU publication?
- yes
- id
- 53eb3a0d-a2ef-4e12-b48b-51f468800383
- date added to LUP
- 2017-03-10 13:31:50
- date last changed
- 2024-01-13 16:47:22
@article{53eb3a0d-a2ef-4e12-b48b-51f468800383,
abstract = {{<p>Neutrophil proteinase 4 (NP4) is a major neutral proteinase of the human polymorphonuclear (PMN) leukocyte, which is present in amounts similar to leukocyte elastase. NP4(3) is a potent, non-specific proteinase, which may degrade structural and soluble proteins in the tissues and body fluids, and it has been implicated as an important pathogenetic factor in lung emphysema. We have studied the release of elastase and NP4(3) in an in vitro model of phagocytosis, α<sub>1</sub>-pproteinase inhibitor (α<sub>1</sub>-PI) is the major plasma inhibitor of both leukocyte elastase and NP4(3), but α<sub>1</sub>-PI bound leukocyte elastase more readily than NP4(3). The basic conditions were designed so that some proteolytic activity was present in the medium. Addition of increasing amounts of Secretory leukocyte protease inhibitor (SLPI) to the incubation mixtures resulted in binding of leukocyte elastase to this inhibitor and extinction of free proteolytic activity against both natural and synthetic substrates. The progressive binding of leukocyte elastase to SLPI instead of α<sub>1</sub>-PI was paralleled by an increasing binding of NP4(3) to α<sub>1</sub>-PI. SLPI is a potent inhibitor of leukocyte elastase and cathepsin G, and although it lacks inhibitory effect on NP4(3), it may obviously indirectly aid in the binding and inhibition of NP4(3) to α<sub>1</sub>-PI, by taking care of at least part of the leukocyte elastase. As a specific NP4(3)-inhibitor is not readily available for therapeutic use, this effect may prove useful under in vivo conditions and enhance the protective effect of administered recombinant human SLPI.</p>}},
author = {{Bergenfeldt, M. and Axelsson, L. and Ohlsson, K.}},
issn = {{0036-5513}},
keywords = {{Leukocyte elastase; Neutrophil proteinase 4; Phagocytosis; Proteinase-3; Secretory leukocyte protease inhibitor}},
language = {{eng}},
number = {{8}},
pages = {{823--829}},
publisher = {{Informa Healthcare}},
series = {{Scandinavian Journal of Clinical and Laboratory Investigation}},
title = {{Release of neutrophil proteinase 4(3) and leukocyte elastase during phagocytosis and their interaction with proteinase inhibitors}},
url = {{http://dx.doi.org/10.3109/00365519209088387}},
doi = {{10.3109/00365519209088387}},
volume = {{52}},
year = {{1992}},
}