New insights into the mechanisms of pulmonary edema in acute lung injury

Herrero, Raquel; Sánchez, Gema; Lorente, José A.

doi:10.21037/atm.2017.12.18

Cited by 198 publications

(196 citation statements)

References 193 publications

(240 reference statements)

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“…As a pivotal autophagy regulator, mTOR is phosphorylated by the activation of the PI3K/Akt pathway [39]. Once mTOR is activated, it can protect pulmonary tissues against, or promote their recovery from, lung injury by reducing autophagy [41,42]. Regarding this, our results showing that BIPM increased levels of p-mTOR/p-PI3K/p-Akt and decreased levels of LC3 II/Beclin 1 indicate that BIPM inhibits excessive autophagy through the activation of the PI3K/Akt/mTOR pathway.…”

Section: Discussionmentioning

confidence: 99%

Biapenem as a Novel Insight into Drug Repositioning against Particulate Matter-Induced Lung Injury

Lee

Baek

Kim

et al. 2020

IJMS

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The screening of biologically active chemical compound libraries can be an efficient way to reposition Food and Drug Adminstration (FDA)-approved drugs or to discover new therapies for human diseases. Particulate matter with an aerodynamic diameter equal to or less than 2.5 μm (PM2.5) is a form of air pollutant that causes significant lung damage when inhaled. This study illustrates drug repositioning with biapenem (BIPM) for the modulation of PM-induced lung injury. Biapenem was used for the treatment of severe infections. Mice were treated with BIPM via tail-vein injection after the intratracheal instillation of PM2.5. Alterations in the lung wet/dry weight, total protein/total cell count and lymphocyte count, inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), vascular permeability, and histology were monitored in the PM2.5-treated mice. BIPM effectively reduced the pathological lung injury, lung wet/dry weight ratio, and hyperpermeability caused by PM2.5. Enhanced myeloperoxidase (MPO) activity by PM2.5 in the pulmonary tissue was inhibited by BIPM. Moreover, increased levels of inflammatory cytokines and total protein by PM2.5 in the BALF were also decreased by BIPM treatment. In addition, BIPM markedly suppressed PM2.5-induced increases in the number of lymphocytes in the BALF. Additionally, the activity of mammalian target of rapamycin (mTOR) was increased by BIPM. Administration of PM2.5 increased the expression levels of toll-like receptor 4 (TLR4), MyD88, and the autophagy-related proteins LC3 II and Beclin 1, which were suppressed by BIPM. In conclusion, these findings indicate that BIPM has a critical anti-inflammatory effect due to its ability to regulate both the TLR4-MyD88 and mTOR-autophagy pathways, and may thus be a potential therapeutic agent against diesel PM2.5-induced pulmonary injury.

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Section: Discussionmentioning

confidence: 99%

Biapenem as a Novel Insight into Drug Repositioning against Particulate Matter-Induced Lung Injury

Lee

Baek

Kim

et al. 2020

IJMS

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“…PE is a common finding in ALI and can cause the lungs to develop into acute respiratory distress syndrome (ARDS) [22]. The activation of lung macrophages and release of cytokines are important mechanisms contributing to lung damage in patients with ARDS [17,23]. Under various triggers, lung macrophages can be polarised into either classically activated (or M1) or alternatively activated (or M2) subtypes [24].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, macrophages can adhere and interact with the epithelium of alveoli resulting in an increase in cytosolic calcium levels which can lead to apoptosis of epithelial cells and the release of TNF-α. This mechanism can further damage the pulmonary barrier resulting in PE [23].…”

Section: Discussionmentioning

confidence: 99%

M1 macrophage activation in severe Plasmodium falciparum malaria patients with pulmonary oedema

Klinkhamhom

Glaharn

Sris

et al. 2020

Preprint

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Background Pulmonary oedema (PE) is a serious complication of severe P. falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarisation is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarisation of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients with and without evidence of PE.Methods Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorised into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68-all macrophages, CD40-M1 macrophage and CD163-M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. ResultsLung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (p < 0.05), whereas there was no difference observed for CD163 (M2 macrophage) between PE and non-PE groups. ConclusionsThe study demonstrates M1 polarisation in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterisation in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria. BackgroundPulmonary oedema (PE) is one of the major complications and therapeutic challenges in severe P. falciparum malaria. This condition is associated with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [1]. The incidence of ARDS in severe P. falciparum patients ranges from 14%-26%, with the mortality rate of 14%-89% [2][3][4]. In addition, PE occurs in approximately 10%-21% [1,5, 6]. In P. falciparum malaria, PE is associated with inflammatory infiltrates consisting of mainly mononuclear cells, haemozoin deposit, the accumulation of macrophages, as well as parasite

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“…In addition, macrophages can adhere and interact with the epithelium of alveoli resulting in an increase in cytosolic calcium levels which can lead to apoptosis of epithelial cells and the release of TNF. This mechanism can further damage the pulmonary barrier resulting in PE [25].…”

Section: Discussionmentioning

confidence: 99%

M1 macrophage features in severe Plasmodium falciparum malaria patients with pulmonary oedema

Klinkhamhom

Glaharn

Sris

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Pulmonary oedema (PE) is a serious complication of Plasmodium falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarization is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarization of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients, with and without evidence of PE.Methods Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorized into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68+, all macrophages; CD40+, M1 macrophage; and CD163+, M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes.Results Lung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (63.44±1.98%), compared to non-PE group (53.22±3.85%, p < 0.05), whereas there was no difference observed for CD163 (M2 macrophage) between PE and non-PE groups.Conclusions The study demonstrates M1 polarization in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterization in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria.

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New insights into the mechanisms of pulmonary edema in acute lung injury

Cited by 198 publications

References 193 publications

Biapenem as a Novel Insight into Drug Repositioning against Particulate Matter-Induced Lung Injury

Biapenem as a Novel Insight into Drug Repositioning against Particulate Matter-Induced Lung Injury

M1 macrophage activation in severe Plasmodium falciparum malaria patients with pulmonary oedema

M1 macrophage features in severe Plasmodium falciparum malaria patients with pulmonary oedema

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