Lung macrophages utilize unique cathepsin K-dependent phagosomal machinery to degrade intracellular collagen

• DOI: 10.1101/2022.05.16.492085
• Publication Date: 2022-05-19T14:37:22Z
• Authors: Ivo Fabrik; Orsolya Bilkei-Gorzo; Daniela Fabrikova; Maria Öberg; Johannes Fuchs; Carina Sihlbom; Melker Göransson; Anetta Härtlova
• Keywords: Proteolysis; Cathepsin K

ABSTRACT Resident tissue macrophages (RTMs) are organ-specialized phagocytes responsible for the maintenance and protection of homeostasis. It is well established that diversity reflected by heterogeneity RTMs origin phenotype. However, much less known about tissue-specific phagocytic proteolytic macrophage functions. Here, using quantitative proteomics approach, we identify cathepsins as key determinants phagosome maturation in primary peritoneal, lung brain resident macrophages. The data further uncover cathepsin K (CtsK) a molecular marker phagosomes required intracellular protein collagen degradation. Pharmacological blockade CtsK activity diminished phagosomal proteolysis collagenolysis Furthermore, pro-fibrotic TGF-β negatively regulated CtsK-mediated degradation independently from classical endocytic pathways. In humans, was reduced COPD non-COPD exposed to cigarette smoke extract. Taken together, this study provides comprehensive map how environment shapes composition, revealing determinant contributing clearance lungs.