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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Life Science Alliance

ISSN

2575-1077

e-ISSN

2575-1077

Svazek periodika

6

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

e202201535

Kód UT WoS článku

000926064800004

EID výsledku v databázi Scopus

2-s2.0-85146862208