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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

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1437-4315
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Volume 397, Issue 9

Issues

Myeloid conditional deletion and transgenic models reveal a threshold for the neutrophil survival factor Serpinb1

Sabrina S. Burgener
  • Theodor Kocher Institute, University of Bern, Freiestrasse 1, CH-3012 Bern, Switzerland
  • Graduate School for Cellular and Biomedical Sciences, University of Bern, CH-3012 Bern, Switzerland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mathias Baumann
  • Theodor Kocher Institute, University of Bern, Freiestrasse 1, CH-3012 Bern, Switzerland
  • Graduate School for Cellular and Biomedical Sciences, University of Bern, CH-3012 Bern, Switzerland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Paola Basilico
  • Theodor Kocher Institute, University of Bern, Freiestrasse 1, CH-3012 Bern, Switzerland
  • Graduate School for Cellular and Biomedical Sciences, University of Bern, CH-3012 Bern, Switzerland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Eileen Remold-O’Donnell
  • Program in Cellular and Molecular Medicine and Division of Hematology/Oncology, Boston Children’s Hospital, Boston, MA 02115, USA
  • Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ivo P. Touw / Charaf BenarafaORCID iD: http://orcid.org/0000-0002-2049-7769
Published Online: 2016-04-22 | DOI: https://doi.org/10.1515/hsz-2016-0132

Abstract

Serpinb1 is an inhibitor of neutrophil granule serine proteases cathepsin G, proteinase-3 and elastase. One of its core physiological functions is to protect neutrophils from granule protease-mediated cell death. Mice lacking Serpinb1a (Sb1a-/-), its mouse ortholog, have reduced bone marrow neutrophil numbers due to cell death mediated by cathepsin G and the mice show increased susceptibility to lung infections. Here, we show that conditional deletion of Serpinb1a using the Lyz2-cre and Cebpa-cre knock-in mice effectively leads to recombination-mediated deletion in neutrophils but protein-null neutrophils were only obtained using the latter recombinase-expressing strain. Absence of Serpinb1a protein in neutrophils caused neutropenia and increased granule permeabilization-induced cell death. We then generated transgenic mice expressing human Serpinb1 in neutrophils under the human MRP8 (S100A8) promoter. Serpinb1a expression levels in founder lines correlated positively with increased neutrophil survival when crossed with Sb1a-/- mice, which had their defective neutrophil phenotype rescued in the higher expressing transgenic line. Using new conditional and transgenic mouse models, our study demonstrates the presence of a relatively low Serpinb1a protein threshold in neutrophils that is required for sustained survival. These models will also be helpful in delineating recently described functions of Serpinb1 in metabolism and cancer.

This article offers supplementary material which is provided at the end of the article.

Keywords: cell death; cre; serine protease; serpin

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About the article

Received: 2016-02-02

Accepted: 2016-04-20

Published Online: 2016-04-22

Published in Print: 2016-09-01


Citation Information: Biological Chemistry, Volume 397, Issue 9, Pages 897–905, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2016-0132.

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