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Neutrophil-derived ...
Neutrophil-derived proteinase 3 induces kallikrein-independent release of a novel vasoactive kinin.
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- Kahn, Robin (author)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Hellmark, Thomas (author)
- Lund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Autoimmunitet och njursjukdomar,Forskargrupper vid Lunds universitet,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Autoimmunity and kidney diseases,Lund University Research Groups
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- Leeb-Lundberg, Fredrik (author)
- Lund University,Lunds universitet,Drug Target Discovery,Forskargrupper vid Lunds universitet,Lund University Research Groups
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Akbari, Nasrin (author)
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Todiras, Mihail (author)
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- Olofsson, Tor (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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- Wieslander, Jörgen (author)
- Lund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Christensson, Anders (author)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups
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- Westman, Kerstin (author)
- Lund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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Bader, Michael (author)
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Müller-Esterl, Werner (author)
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- Karpman, Diana (author)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Pediatrisk nefrologi,Forskargrupper vid Lunds universitet,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Pediatric Nephrology,Lund University Research Groups
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(creator_code:org_t)
- The American Association of Immunologists, 2009
- 2009
- English.
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In: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 182:12, s. 7906-7915
- Related links:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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http://www.jimmunol....
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https://lup.lub.lu.s...
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https://doi.org/10.4...
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Abstract
Subject headings
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- The kinin-forming pathway is activated on endothelial cells and neutrophils when high-molecular weight kininogen (HK) is cleaved by plasma kallikrein liberating bradykinin, a potent mediator of inflammation. Kinins are released during inflammatory conditions such as vasculitis, associated with neutrophil influx around blood vessels. Some patients with vasculitis have elevated plasma levels of neutrophil-derived proteinase 3 (PR3) and anti-PR3 Abs. This study investigated if neutrophil-derived PR3 could induce activation of the kinin pathway. PR3 incubated with HK, or a synthetic peptide derived from HK, induced breakdown and release of a novel tridecapeptide termed PR3-kinin, NH(2)-MKRPPGFSPFRSS-COOH, consisting of bradykinin with two additional amino acids on each terminus. The reaction was specific and inhibited by anti-PR3 and alpha(1)-antitrypsin. Recombinant wild-type PR3 incubated with HK induced HK breakdown, whereas mutated PR3, lacking enzymatic activity, did not. PR3-kinin bound to and activated human kinin B(1) receptors, but did not bind to B(2) receptors, expressed by transfected HEK293 cells in vitro. In human plasma PR3-kinin was further processed to the B(2) receptor agonist bradykinin. PR3-kinin exerted a hypotensive effect in vivo through both B(1) and B(2) receptors as demonstrated using wild-type and B(1) overexpressing rats as well as wild-type and B(2) receptor knockout mice. Neutrophil extracts from vasculitis patients and healthy controls contained comparable amounts of PR3 and induced HK proteolysis, an effect that was abolished when PR3 was immunoadsorbed. Neutrophil-derived PR3 can proteolyze HK and liberate PR3-kinin, thereby initiating kallikrein-independent activation of the kinin pathway.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Neutrophils: enzymology
- Myeloblastin: metabolism
- Myeloblastin: genetics
- Kinins: secretion
- Kininogens: metabolism
- Bradykinin: blood
- Kallikreins: metabolism
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Kahn, Robin
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Hellmark, Thomas
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Leeb-Lundberg, F ...
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Akbari, Nasrin
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Todiras, Mihail
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Olofsson, Tor
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show more...
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Wieslander, Jörg ...
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Christensson, An ...
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Westman, Kerstin
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Bader, Michael
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Müller-Esterl, W ...
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Karpman, Diana
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Journal of immun ...
- By the university
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Lund University