PXD033010-2

PXD033010 is an original dataset announced via ProteomeXchange.

Title	Lung macrophages utilize unique cathepsin K-dependent phagosomal machinery to degrade intracellular collagen
Description	Resident tissue macrophages (RTMs) are organ-specialized phagocytes responsible for the maintenance and protection of residing tissue. It is well established that tissue diversity is reflected by the heterogeneity of RTMs origin and phenotype. However, much less is known about tissue-specific phagocytic macrophage functions. Here, using quantitative proteomics approach, we identify cathepsins as key determinants of phagosome maturation in primary peritoneal, lung and brain resident macrophages. The data further uncover cathepsin K (CtsK) as a molecular marker for lung phagosomes required for intracellular protein and collagen degradation. Pharmacological blockade of CtsK activity diminished phagosomal proteolysis and collagenolysis in lung resident macrophages. Furthermore, pro-fibrotic TGF-β negatively regulated CtsK-mediated phagosomal collagen degradation independently from classical endocytic proteolytic pathways. In humans, phagosomal CtsK activity was reduced in lung COPD macrophages and lung macrophages exposed to cigarette smoke extract. Taken together, this study provides a comprehensive map of how peritoneal, lung and brain tissue environment shapes phagosomal composition of resident macrophages, revealing CtsK as a key molecular determinant of lung phagosomes contributing to phagocytic collagen clearance in lungs.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:20.215.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ivo Fabrik
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-06 08:11:06	ID requested
1	2023-01-17 23:47:38	announced
⏵ 2	2023-11-14 08:55:20	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: phagocytosis, proteomics,Cathepsins, resident tissue macrophages, phagosome maturation

Anetta Härtlova
contact affiliation	Institute of Biomedicine, Department of Microbiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
contact email	anetta.hartlova@gu.se
lab head
Ivo Fabrik
contact affiliation	Biomedical Research Center, University Hospital Hradec Kralove
contact email	ivo.fabrik@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/01/PXD033010

PRIDE project URI

• PRIDE
  1. PXD033010
     1. Label: PRIDE project
     2. Name: Lung macrophages utilize unique cathepsin K-dependent phagosomal machinery to degrade intracellular collagen