PMID- 38260346
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240429
DP  - 2024 Jan 4
TI  - Air pollution drives macrophage senescence through a 
      phagolysosome-15-lipoxygenase pathway.
LID - 2024.01.04.574228 [pii]
LID - 10.1101/2024.01.04.574228 [doi]
AB  - Urban particulate matter (uPM) poses significant health risks, particularly to 
      the respiratory system. Fine particles, such as PM(2.5), can penetrate deep into 
      the lungs and exacerbate a range of health problems, including emphysema, asthma, 
      and lung cancer. PM exposure is also linked to extra-pulmonary disorders like 
      heart and neurodegenerative diseases. Moreover, prolonged exposure to elevated PM 
      levels can reduce overall life expectancy. Senescence is a dysfunctional cell 
      state typically associated with age but can also be precipitated by environmental 
      stressors. This study aimed to determine whether uPM could drive senescence in 
      macrophages, an essential cell type involved in particulate phagocytosis-mediated 
      clearance. While it is known that uPM exposure impairs immune function, this 
      deficit is multi-faceted and incompletely understood, partly due to the use of 
      particulates such as diesel exhaust particle (DEP) as a surrogate for true uPM. 
      uPM was collected from several locations in the USA, including Baltimore, 
      Houston, and Phoenix. Bone marrow-derived macrophages (BMDMs) were stimulated 
      with uPM or reference particulates (e.g., DEP) to assess senescence-related 
      parameters. We report that uPM-exposed BMDMs adopt a senescent phenotype 
      characterized by increased IL-1alpha secretion, senescence-associated beta-galactosidase 
      activity, and diminished proliferation. Exposure to allergens failed to elicit 
      such a response, supporting a distinction between different types of 
      environmental exposures. uPM-induced senescence was independent of key macrophage 
      activation pathways, specifically inflammasome and scavenger receptor. However, 
      inhibition of the phagolysosome pathway abrogated senescence markers, supporting 
      this phenotype's attribution to uPM phagocytosis. These data suggest uPM exposure 
      leads to macrophage senescence, which may contribute to immunopathology.
FAU - Thomas, Sarah A
AU  - Thomas SA
AD  - W. Harry Feinstone Department of Molecular Microbiology & Immunology, Johns 
      Hopkins Bloomberg School of Public Health, Baltimore, MD.
FAU - Yong, Hwan Mee
AU  - Yong HM
AD  - Department of Environmental Health and Engineering, Johns Hopkins Bloomberg 
      School of Public Health, Baltimore, MD.
FAU - Rule, Ana M
AU  - Rule AM
AD  - Department of Environmental Health and Engineering, Johns Hopkins Bloomberg 
      School of Public Health, Baltimore, MD.
FAU - Gour, Naina
AU  - Gour N
AD  - Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, 
      Baltimore, MD.
FAU - Lajoie, Stephane
AU  - Lajoie S
AD  - Department of Otolaryngology, Johns Hopkins School of Medicine, Baltimore, MD.
LA  - eng
GR  - R01 AI170709/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20240104
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
UIN - Immunohorizons. 2024 Apr 1;8(4):307-316. PMID: 38625119
PMC - PMC10802326
OTO - NOTNLM
OT  - air pollution
OT  - macrophages
OT  - particulate matter
OT  - senescence
EDAT- 2024/01/23 12:43
MHDA- 2024/01/23 12:44
PMCR- 2024/01/22
CRDT- 2024/01/23 10:36
PHST- 2024/01/23 12:43 [pubmed]
PHST- 2024/01/23 12:44 [medline]
PHST- 2024/01/23 10:36 [entrez]
PHST- 2024/01/22 00:00 [pmc-release]
AID - 2024.01.04.574228 [pii]
AID - 10.1101/2024.01.04.574228 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2024 Jan 4:2024.01.04.574228. doi: 10.1101/2024.01.04.574228.