Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes

Bos, Lieuwe; Ware, Lorraine B.

doi:10.1016/s0140-6736(22)01485-4

Cited by 290 publications

(165 citation statements)

References 118 publications

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“…Excessive inflammatory responses are generally considered the major underlying pathogenesis of ARDS (2). Therefore, we detected the number of exudated inflammatory cells and cytokine levels in BALF.…”

Section: Pe Ameliorated Lung Inflammation In Ards Micementioning

confidence: 99%

“…Acute respiratory distress syndrome (ARDS) is a common critical illness characterized by acute hypoxic respiratory insufficiency or failure, often requiring hospitalisation in an intensive care unit (1). The life-threatening illness can be caused by a variety of non-cardiogenic factors, including pneumonia, sepsis, and trauma (2). Because of its multifactorial aetiology and complex pathogenesis, ARDS shows great heterogeneity across different subpopulations of patients (3).…”

Section: Introductionmentioning

confidence: 99%

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α1-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS

Cong

Yang²,

Zeng³

et al. 2023

Front. Immunol.

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IntroductionCatecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating adrenergic receptors (ARs). But the role of α1-AR in this process has yet to be elucidated.MethodsIn this study, ARDS mouse model was induced by intratracheal instillation of lipopolysaccharide. After treatment with α1-AR agonist phenylephrine or antagonist prazosin, lung pathological injury, alveolar barrier disruption and inflammation, and haemodynamic changes were evaluated. Cytokine levels and cell viability of alveolar macrophages were measured in vitro. Nuclear factor κB (NF-κB), mitogen-activated protein kinase, and Akt signalling pathways were analysed by western blot.ResultsIt showed that α1-AR activation alleviated lung injuries, including reduced histopathological damage, cytokine expression, and inflammatory cell infiltration, and improved alveolar capillary barrier integrity of ARDS mice without influencing cardiovascular haemodynamics. In vitro experiments suggested that α1-AR stimulation inhibited secretion of TNF-α, IL-6, CXCL2/MIP-2, and promoted IL-10 secretion, but did not affect cell viability. Moreover, α1-AR stimulation inhibited NF-κB and enhanced ERK1/2 activation without significantly influencing p38, JNK, or Akt activation.DiscussionOur studies reveal that α1-AR stimulation could ameliorate lipopolysaccharide-induced lung injury by inhibiting NF-κB and promoting ERK1/2 to suppress excessive inflammatory responses of alveolar macrophages.

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Section: Pe Ameliorated Lung Inflammation In Ards Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

α1-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS

Cong

Yang²,

Zeng³

et al. 2023

Front. Immunol.

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“…Acute respiratory distress syndrome (ARDS) is a clinical syndrome with a complex pathophysiology that involves dysregulation and activation of multiple pathways of inflammation, coagulation, and injury in the lung. The multiple causes for the development of ARDS in combination with clinical and biological heterogeneity suggest that ARDS is an umbrella term that includes multiple phenotypes ( 24 ). These different phenotypes might be one of many factors responsible for the lack of improved outcome in clinical MSC trials of ARDS.…”

Section: The Diseased Lung Microenvironment and Its Effect On Msc Fun...mentioning

confidence: 99%

“…Diffuse alveolar damage characterized by hyaline membrane deposition and neutrophilic alveolitis is one of the classical pathological findings in the ARDS lung identified post mortem in approximately 45% of the ARDS patients ( 25 , 26 ). Moreover, injury to both the alveolar barrier and the capillary barrier is common in ARDS ( 25 ) and contributes to paracellular permeability, impaired fluid clearance [reviewed in ( 27 )], impaired surfactant production ( 28 ), shedding of anticoagulant molecules and tissue factors ( 29 , 30 ), and intensification of pro-inflammatory signaling [reviewed in ( 24 )]. Taken together, these different pathophysiological findings in ARDS patients contribute to a complex inflammatory and severe edema host microenvironment ( Figure 2B ), that will most likely have a major effect on MSC biology and function.…”

Section: The Diseased Lung Microenvironment and Its Effect On Msc Fun...mentioning

confidence: 99%

MSCs interaction with the host lung microenvironment: An overlooked aspect?

Weiss

Enes

2022

Front. Immunol.

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Mesenchymal stromal cells (MSCs) were identified more than 50 years ago, and research advances have promoted the translation of pre-clinical studies into clinical settings in several diseases. However, we are only starting to uncover the local factors that regulate cell phenotype, cell function, and cell viability across tissues following administration in different diseases. Advances in pre-clinical and translational studies suggest that the host environment, especially inflammatory active environments, plays a significant role in directing the infused MSCs towards different phenotypes with different functions. This can significantly effect their therapeutic efficacy. One way to study this interaction between the host environment and the infused cells is to expose MSCs ex vivo to patient samples such as serum or bronchoalveolar lavage fluid. Using this approach, it has been demonstrated that MSCs are very sensitive to different host factors such as pathogens, inflammatory cytokines, and extra cellular matrix properties. By understanding how different local host factors effect MSC function it will open possibilities to select specific patient sub-groups that are more likely to respond to this type of treatment and will also open possibilities to prime the local host environment to increase viability and to enrich for a specific MSC phenotype. Here, we aim to review the current understanding of the interaction of MSCs with the host microenvironment. To narrow the scope of this mini review, the focus will be on the pulmonary microenvironment, with a specific focus on the diseases acute respiratory distress syndrome (ARDS) and cystic fibrosis (CF).

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“…Acute lung injury (ALI), a progressive life-threatening clinical condition, is characterized by local inflammatory accumulation, the elevated penetrability of the alveolar-capillary barrier, denudation of the alveolar epithelium, and pulmonary edema [1]. Particularly pro-inflammatory cascade response plays an essential role in the pathogenesis of ALI [2]. Alveolar macrophages (AMs) account for approximately 95% of airspace leukocytes [3].…”

Section: Introductionmentioning

confidence: 99%

TREM-1 triggers necroptosis of macrophages through mTOR-dependent mitochondrial fission during acute lung injury

Zhong

Zhang

Duan

et al. 2023

Preprint

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Background Necroptosis of macrophage plays an essential role in amplifying intrapulmonary inflammation during acute lung injury (ALI). However, the molecular mechanism that triggers macrophage necroptosis is still unclear. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor expressed broadly on monocytes/macrophages. The role of TREM-1 in macrophage fate during ALI needs further investigation. Methods TREM-1 decoy receptor LR12 was used to evaluate whether the TREM-1 activation induced necroptosis of macrophages in lipopolysaccharide (LPS)-induced ALI in mice. Then we used an agonist anti-TREM-1 Ab (Mab1187) to activate TREM-1 in vitro. Mechanistically, macrophages were treated with RIPK3 inhibitor (GSK872), GTPase dynamin-related protein 1 (DRP1) inhibitor (Mdivi-1), or the nutrient-sensing mechanistic/mammalian target of rapamycin complex (mTOR) inhibitor (Rapamycin) to investigate macrophage necroptosis induced by TREM-1. Results We first observed that blockade of TREM-1 attenuated macrophage necroptosis in LPS-induced ALI mice. In vitro, TREM-1 activation induced necroptosis of macrophages. mTOR has been previously linked to macrophage polarization and migration. Interestingly, we identified a previously unknown role of mTOR in regulating TREM-1-mediated mitochondrial fission, mitophagy, and necroptosis. Moreover, TREM-1 activation promoted DRP1Ser616 phosphorylation via mTOR signaling, leading to excessive mitochondrial fission-mediated necroptosis of macrophages, and finally exacerbated ALI. Conclusion In this study, we reported TREM-1 acted as a necroptotic stimulus of macrophage, which fueled inflammation and aggravated ALI. We also provided compelling evidence suggesting mTOR-dependent mitochondrial fission as underpinnings of TREM-1-triggered necroptosis and inflammation. Therefore, regulation of necroptosis by targeting TREM-1 may provide a new therapeutic target for ALI in the future.

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Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes

Cited by 290 publications

References 118 publications

α1-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS

α1-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS

MSCs interaction with the host lung microenvironment: An overlooked aspect?

TREM-1 triggers necroptosis of macrophages through mTOR-dependent mitochondrial fission during acute lung injury

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