Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

 
 
DownloadE-Mail
  Unopposed Cathepsin G, Neutrophil Elastase, and Proteinase 3 Cause Severe Lung Damage and Emphysema

Guyot, N., Wartelle, J., Malleret, L., Todorov, A. A., Devouassoux, G., Pacheco, Y., et al. (2014). Unopposed Cathepsin G, Neutrophil Elastase, and Proteinase 3 Cause Severe Lung Damage and Emphysema. AMERICAN JOURNAL OF PATHOLOGY, 184(8), 2197-2210. doi:10.1016/j.ajpath.2014.04.015.

Item is

Externe Referenzen

einblenden:

Urheber

einblenden:
ausblenden:
 Urheber:
Guyot, Nicolas1, Autor
Wartelle, Julien1, Autor
Malleret, Laurette1, Autor
Todorov, Alexandre A.1, Autor
Devouassoux, Gilles1, Autor
Pacheco, Yves1, Autor
Jenne, Dieter E.2, Autor           
Belaaouaj, Azzaq1, Autor
Affiliations:
1external, ou_persistent22              
2Research Group: Enzymes and Inhibitors in Chronic Lung Disease / Jenne, MPI of Neurobiology, Max Planck Society, ou_1950284              

Inhalt

einblenden:
ausblenden:
Schlagwörter: OBSTRUCTIVE PULMONARY-DISEASE; SMOKE-INDUCED EMPHYSEMA; PSEUDOMONAS-AERUGINOSA; LEUKOCYTE ELASTASE; SERINE PROTEASES; HOST-DEFENSE; NONOXIDATIVE MECHANISM; DEFICIENT MICE; GELATINASE B; INFLAMMATION
 Zusammenfassung: Cigarette smoking is a major factor for the development of pulmonary emphysema because it induces abnormal inflammation and a protease-rich local milieu that causes connective tissue breakdown of the Lungs. As a result of its capacity to degrade Lung tissue and the high risk of patients lacking alpha(1)-antitrypsin to develop emphysema, much interest has focused on neutrophil elastase (NE). Two similar neutrophil serine proteases (NSPs), cathepsin G and proteinase 3, coexist with NE in humans and mice, but their potential tissue-destructive role(s) remains unclear. Using a gene-targeting approach, we observed that in contrast to their wild-type Littermates, mice deficient in all three NSPs were substantially protected against Lung tissue destruction after long-term exposure to cigarette smoke. In exploring the underlying basis for disrupted wild-type Lung air spaces, we found that active NSPs collectively caused more severe lung damage than did NE alone. Furthermore, NSP activities unleashed increased activity of the tissue-destructive proteases macrophage elastase (matrix metalloproteinase-12) and gelatinase B (matrix metalloproteinase-9). These in vivo data provide, for the first time, compelling evidence of the collateral involvement of cathepsin G, NE, and proteinase 3 in cigarette smoke induced tissue damage and emphysema. They also reveal a complex positive feed-forward loop whereby these NSPs induce the destructive potential of other proteases, thereby generating a chronic and pathogenic protease-rich milieu.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 2014-08
 Publikationsstatus: Erschienen
 Seiten: 14
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: ISI: 000339533100007
DOI: 10.1016/j.ajpath.2014.04.015
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: AMERICAN JOURNAL OF PATHOLOGY
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA : ELSEVIER SCIENCE INC
Seiten: - Band / Heft: 184 (8) Artikelnummer: - Start- / Endseite: 2197 - 2210 Identifikator: ISSN: 0002-9440