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Release of neutrophil proteinase 4(3) and leukocyte elastase during phagocytosis and their interaction with proteinase inhibitors

Bergenfeldt, M. LU ; Axelsson, L. LU and Ohlsson, K. (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.

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author
organization
publishing date
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
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
2017-03-26 04:50:42
@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},
  keyword      = {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},
  volume       = {52},
  year         = {1992},
}