Lung macrophages utilize unique cathepsin K-dependent phagosomal machinery to degrade intracellular collagen
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F23%3A10458135" target="_blank" >RIV/00179906:_____/23:10458135 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3Bp4ZKa7G-" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3Bp4ZKa7G-</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.26508/lsa.202201535" target="_blank" >10.26508/lsa.202201535</a>
Alternative languages
Result language
angličtina
Original language name
Lung macrophages utilize unique cathepsin K-dependent phagosomal machinery to degrade intracellular collagen
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Life Science Alliance
ISSN
2575-1077
e-ISSN
2575-1077
Volume of the periodical
6
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
e202201535
UT code for WoS article
000926064800004
EID of the result in the Scopus database
2-s2.0-85146862208