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Lung macrophages ut...
Lung macrophages utilize unique cathepsin K-dependent phagosomal machinery to degrade intracellular collagen
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- Fabrik, Ivo (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Bilkei-Gorzo, Orsolya (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Wallenberg Centre for Molecular and Translational Medicine,Institute of Biomedicine, Department of Microbiology and Immunology
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- Öberg, Maria (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Fabrikova, Daniela (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Fuchs, Johannes (författare)
- Gothenburg University,Göteborgs universitet,Core Facilities, Proteomics,Core Facilities, Proteomics
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- Sihlbom, Carina, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Core Facilities, Proteomics,Core Facilities, Proteomics
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Goransson, M. (författare)
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- Härtlova, Anetta (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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(creator_code:org_t)
- 2023-01-25
- 2023
- Engelska.
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Ingår i: Life Science Alliance (LSA). - : Life Science Alliance, LLC. - 2575-1077. ; 6:4
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- Resident tissue macrophages are organ-specialized phagocytes responsible for the maintenance and protection of tissue ho-meostasis. It is well established that tissue diversity is reflected by the heterogeneity of resident tissue macrophage origin and phenotype. However, much less is known about tissue-specific phagocytic and proteolytic macrophage functions. Here, using a quantitative proteomics approach, we identify cathepsins as key determinants of phagosome maturation in primary peritoneum-, 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 phag-osomal proteolysis and collagenolysis in lung-resident mac-rophages. Furthermore, profibrotic TGF-beta negatively regulated CtsK-mediated phagosomal collagen degradation indepen-dently from classical endocytic-proteolytic pathways. In humans, phagosomal CtsK activity was reduced in COPD lung macrophages and non-COPD lung macrophages exposed to cig-arette smoke extract. Taken together, this study provides a comprehensive map of how peritoneal, lung, and brain tissue environment shapes phagosomal composition, revealing CtsK as a key molecular determinant of lung phagosomes contributing to phagocytic collagen clearance in lungs.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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