Authors:	Alflen, Astrid Prüfer, Steve Ebner, Katharina Reuter, Sebastian Lopez, Pamela Aranda Scharrer, Inge Banno, Fumiaki Stassen, Michael Schild, Hansjörg Jurk, Kerstin Bosmann, Markus Beckert, Hendrik Radsak, Markus
Title:	ADAMTS-13 regulates neutrophil recruitment in a mouse model of invasive pulmonary aspergillosis
Online publication date:	12-Jul-2022
Year of first publication:	2017
Language:	english
Abstract:	Von Willebrand factor (VWF) is secreted as an acute phase protein during inflammation. ADAMTS-13 regulates the size and prothrombotic activity of VWF by it’s specific proteolytic activity. To determine the relevance of this regulatory pathway for the innate inflammatory response by polymorphonuclear neutrophils (PMN), we employed a mouse model of invasive pulmonary aspergillosis (IPA) where PMN functionality is crucial for fungal clearance and survival. IPA was induced by intratracheal application of Aspergillus fumigatus (A. fumigatus) conidia in wildtype (129/Sv/Pas) or ADAMTS-13 deficient (Adamts13−/−) mice. While neutropenic mice developed lethal IPA, all wildtype mice survived the infection. In contrast to wildtype or VWF deficient mice, Adamts13−/− mice displayed more severe signs of disease with a lethal course in 24% with an increased fungal burden and signs of acute lung injury. Histology sections demonstrated a more pronounced perivascular leukocyte infiltration in support of a dysregulated inflammatory response in Adamts13−/− mice. Importantly, we observed no general defect in the activation of neutrophil functions in response to conidia or hyphae in vitro. Therefore, we conclude that the proteolytic regulation of VWF by ADAMTS-13 or ADAMTS-13 by itself is an important mechanism to control PMN recruitment in acute inflammatory processes, such as fungal pneumonias.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7361
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Scientific reports 7
Pages or article number:	Art. 7184
Publisher:	Macmillan Publishers Limited, part of Springer Nature
Publisher place:	London
Issue date:	2017
ISSN:	2045-2322
Publisher URL:	http://dx.doi.org/10.1038/s41598-017-07340-3
Publisher DOI:	10.1038/s41598-017-07340-3
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)