PMID- 33235481
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220418
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 13
DP  - 2020
TI  - Human Lung Macrophages Challenged to Oxidants ex vivo: Lysosomal Membrane 
      Sensitization is Associated with Inflammation and Chronic Airflow Limitation.
PG  - 925-932
LID - 10.2147/JIR.S280419 [doi]
AB  - BACKGROUND: The lung macrophage (LM) is involved in most inflammatory processes 
      of the human lung by clearance of dying cells and by wound repair. Upon cellular 
      stress by oxidant challenge in vivo lysosomes may rupture in LMs and leakage of 
      cellular content and cell debris may trigger airway inflammation and fibrosis, 
      which may lead to chronic airflow limitation (CAL). OBJECTIVE: The aim of this 
      study was to determine whether lysosomal membrane permeabilization (LMP) in LMs 
      challenged to oxidants ex vivo is associated with airway inflammation and CAL, 
      the latter assessed as the reduced forced expiratory volume in one second 
      (FEV(1)) expressed as % of predicted. MATERIALS AND METHODS: Twenty-eight 
      subjects were investigated; 13 lung-healthy subjects and 15 subjects with a 
      variety of inflammatory disorders, demonstrating CAL on dynamic spirometry 
      (defined as an FEV(1)/FVC ratio < 0.70). LMs were harvested by broncho-alveolar 
      lavage (BAL) and challenged ex vivo by oxidants. LMP in oxidant-exposed LMs was 
      assessed as the emitted acridine orange (AO) green fluorescence from 
      oxidant-exposed LMs (using macrophage-like murine J774 cells as positive 
      controls). Inflammatory cells in BAL were counted and lung volumes were recorded. 
      RESULTS: Oxidant-induced LMP in LMs was significantly greater among subjects with 
      CAL and particularly among those with ongoing inflammation. Previous tobacco 
      history did not influence LMP. Among subjects with CAL, oxidant-induced LMP 
      correlated negatively with FEV(1)% of predicted. CONCLUSION: Lysosomes of LMs 
      harvested from patients with CAL demonstrate an increased sensitivity to 
      oxidants, which may trigger mechanisms behind CAL, eg, chronic airway 
      inflammation and fibrotic re-modelling. The study suggests a mechanistic role for 
      LMP in LMs on airway inflammation, suggesting an anti-inflammatory effect by 
      drugs that prevent increased LMP.
CI  - (c) 2020 Persson et al.
FAU - Persson, Hans Lennart
AU  - Persson HL
AUID- ORCID: 0000-0002-5700-7284
AD  - Department of Respiratory Medicine in Linkoping, Linkoping University, Linkoping, 
      Sweden.
AD  - Department of Health, Medicine and Caring Sciences, Linkoping University, 
      Linkoping, Sweden.
FAU - Sioutas, Apostolos
AU  - Sioutas A
AD  - Department of Respiratory Medicine in Linkoping, Linkoping University, Linkoping, 
      Sweden.
AD  - Department of Health, Medicine and Caring Sciences, Linkoping University, 
      Linkoping, Sweden.
FAU - Jacobson, Petra
AU  - Jacobson P
AD  - Department of Respiratory Medicine in Linkoping, Linkoping University, Linkoping, 
      Sweden.
AD  - Department of Health, Medicine and Caring Sciences, Linkoping University, 
      Linkoping, Sweden.
FAU - Vainikka, Linda K
AU  - Vainikka LK
AUID- ORCID: 0000-0002-4371-1238
AD  - Department of Experimental Pathology, Linkoping University, Linkoping, Sweden.
AD  - Department of Biomedical and Clinical Sciences, Linkoping University, Linkoping, 
      Sweden.
LA  - eng
PT  - Journal Article
DEP - 20201116
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC7678820
OTO - NOTNLM
OT  - BAL
OT  - COPD
OT  - LMP
OT  - acridine orange
OT  - lung macrophages
OT  - pulmonary fibrosis
COIS- The authors have no financial or non-financial conflicts to disclose in relation 
      to the present study.
EDAT- 2020/11/26 06:00
MHDA- 2020/11/26 06:01
PMCR- 2020/11/16
CRDT- 2020/11/25 05:45
PHST- 2020/09/04 00:00 [received]
PHST- 2020/10/20 00:00 [accepted]
PHST- 2020/11/25 05:45 [entrez]
PHST- 2020/11/26 06:00 [pubmed]
PHST- 2020/11/26 06:01 [medline]
PHST- 2020/11/16 00:00 [pmc-release]
AID - 280419 [pii]
AID - 10.2147/JIR.S280419 [doi]
PST - epublish
SO  - J Inflamm Res. 2020 Nov 16;13:925-932. doi: 10.2147/JIR.S280419. eCollection 
      2020.