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PMID: 3198760 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters.

The Journal of clinical investigation ·Vol. 82 ·No. 6 ·1988-12-00 ·Pages 1963-73

Kao RC, Wehner NG, Skubitz KM, Gray BH, Hoidal JR

Abstract

Studies were designed to explore the possibility that human polymorphonuclear leukocyte granule constituents in addition to elastase (HLE) had the potential to cause emphysema. A two-step purification of three serine proteinases was developed. Granule extract proteins were initially separated by dye-ligand affinity chromatography. Fractions eluted were divided into four pools. Hamsters were given a single intratracheal instillation of saline +/- 0.1 mg protein of each pool. While pool 2 contained HLE and cathepsin G, the most dramatic bullous emphysema developed in animals treated with pool 4. The esterase from pool 4, designated proteinase 3 (PR-3) was purified, characterized in vitro, and tested for its ability to cause emphysema. PR-3 is a neutral serine proteinase with isoenzyme forms. Its ability to degrade elastin at pH 6.5 is slightly greater than that of HLE, but it is less active than HLE at pH 7.4 or 8.9. PR-3 has weak activity against azocasein. Its ability to degrade hemoglobin is intermediate to that of HLE and cathepsin G at pH 7.4. PR-3 has no activity against chromogenic substrates specific for HLE or cathepsin G. Its pI is substantially less than HLE or cathepsin G. It is also immunologically distinct from HLE. It induces emphysema in hamsters commensurate with that of HLE. We conclude that PR-3 may be important in the pathogenesis of human emphysema.

MeSH Terms
Animals Cathepsin G Cathepsins/metabolism Cricetinae Elastin/metabolism Emphysema/enzymology Humans Leukocyte Elastase Myeloblastin Naphthols/metabolism Neutrophils/enzymology Pancreatic Elastase/metabolism Serine Endopeptidases/blood,isolation & purification
Chemicals
Naphthols alpha-naphthyl acetate Elastin Cathepsins Serine Endopeptidases CTSG protein, human Cathepsin G Pancreatic Elastase Leukocyte Elastase Myeloblastin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kao R C
Department of Microbiology, University of Minnesota, Minneapolis 55455.
Wehner N G
Skubitz K M
Gray B H
Hoidal J R
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI113816
Published
1988-12-00
Pages
1963-73
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC442778
Subset
IM
Grants
NHLBI NIH HHS · HL-01308 · United States
NHLBI NIH HHS · HL-32329 · United States
NHLBI NIH HHS · HL-37615 · United States
External Links
PubMed source DOI: 10.1172/JCI113816 PMC Full Text View journal details
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