scholarly journals Secretory Autophagosomes from Alveolar Macrophages Exacerbate Acute Respiratory Distress Syndrome by Releasing IL-1β

2022 ◽  
Vol Volume 15 ◽  
pp. 127-140
Author(s):  
Xinyi Xu ◽  
Xu Liu ◽  
Xuecheng Dong ◽  
Haibo Qiu ◽  
Yi Yang ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Alveolar Macrophages ◽  
Distress Syndrome

Clinical and pathological features of fat embolism with acute respiratory distress syndrome

2007 ◽  
Vol 113 (6) ◽  
pp. 279-285 ◽  
Author(s):  
Shang Jyh Kao ◽  
Diana Yu-Wung Yeh ◽  
Hsing I. Chen
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Partial Pressure ◽  
Alveolar Macrophages ◽  
Distress Syndrome ◽  
Fat Embolism ◽  
Arterial Partial Pressure ◽  
Arterial Blood ◽  
Blood Ph

FES (fat embolism syndrome) is a clinical problem, and, although ARDS (acute respiratory distress syndrome) has been considered as a serious complication of FES, the pathogenesis of ARDS associated with FES remains unclear. In the present study, we investigated the clinical manifestations, and biochemical and pathophysiological changes, in subjects associated with FES and ARDS, to elucidate the possible mechanisms involved in this disorder. A total of eight patients with FES were studied, and arterial blood pH, PaO2 (arterial partial pressure of O2), PaCO2 (arterial partial pressure of CO2), biochemical and pathophysiological data were obtained. These subjects suffered from crash injuries and developed FES associated with ARDS, and each died within 2 h after admission. In the subjects, chest radiography revealed that the lungs were clear on admission, and pulmonary infiltration was observed within 2 h of admission. Arterial blood pH and PaO2 declined, whereas PaCO2 increased. Plasma PLA2 (phospholipase A2), nitrate/nitrite, methylguanidine, TNF-α (tumour necrosis factor-α), IL-1β (interleukin-1β) and IL-10 (interleukin-10) were significantly elevated. Pathological examinations revealed alveolar oedema and haemorrhage with multiple fat droplet depositions and fibrin thrombi. Fat droplets were also found in the arterioles and/or capillaries in the lung, kidney and brain. Immunohistochemical staining identified iNOS (inducible nitric oxide synthase) in alveolar macrophages. In conclusion, our clinical analysis suggests that PLA2, NO, free radicals and pro-inflammatory cytokines are involved in the pathogenesis of ARDS associated with FES. The major source of NO is the alveolar macrophages.

scholarly journals α2A-adrenoceptor deficiency attenuates lipopolysaccharide-induced lung injury by increasing norepinephrine levels and inhibiting alveolar macrophage activation in acute respiratory distress syndrome

2020 ◽  
Vol 134 (14) ◽  
pp. 1957-1971 ◽  
Author(s):  
Zhukai Cong ◽  
Dan Li ◽  
Xiangpeng Lv ◽  
Cui Yang ◽  
Qiang Zhang ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Alveolar Macrophages ◽  
Distress Syndrome ◽  
High Morbidity ◽  
Research Attention ◽  
Tnf Α

Abstract Acute respiratory distress syndrome (ARDS) is a severe condition with high morbidity and mortality and few interventions. The role of sympathetic stress in the pathogenesis of ARDS has attracted recent research attention. Blockade of α-2 or α2A-adrenoceptor (α2A-AR) has been shown to attenuate lung injury induced by lipopolysaccharide (LPS) in rats. However, the mechanism is unclear. We confirmed the role of α2A-AR in ARDS using knockout mice and alveolar macrophages following LPS stimulation to assess the underlying mechanisms. We found that α2A-AR deficiency decreased the permeability of the alveolar capillary barrier in ARDS mice and suppressed lung inflammation by reducing inflammatory cell infiltration and the production of TNF-α, interleukin (IL)-6, and CXCL2/MIP-2. LPS stimulation decreased NF-κB activation in lung tissues of α2A-AR deficient mice and increased norepinephrine concentrations. In vitro, we found that norepinephrine inhibited the production of TNF-α, IL-6, and CXCL2/MIP-2 and promoted the secretion of IL-10 from LPS-stimulated murine alveolar macrophages. Blockade of α2A-AR by a specific antagonist further inhibited the production of TNF-α, IL-6, and IL-10. Furthermore, norepinephrine down-regulated NF-κB activation in stimulated alveolar macrophages. Altogether, these results suggest that α2A-AR deficiency ameliorates lung injury by increasing norepinephrine concentrations in lung tissues and inhibiting the activation of alveolar macrophages.

Osteopontin is Strongly Expressed by Alveolar Macrophages in the Lungs of Acute Respiratory Distress Syndrome

Lung ◽  
2004 ◽  
Vol 182 (3) ◽  
Author(s):  
Fumiyuki Takahashi ◽  
Kazuhisa Takahashi ◽  
Kazue Shimizu ◽  
Ri Cui ◽  
Norihiro Tada ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Alveolar Macrophages ◽  
Distress Syndrome

NF-κB REGULATORY MECHANISMS IN ALVEOLAR MACROPHAGES FROM PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME

Shock ◽  
2000 ◽  
Vol 13 (2) ◽  
pp. 85-91 ◽  
Author(s):  
Pierre Moine ◽  
Robert McIntyre ◽  
Michael D. Schwartz ◽  
Debra Kaneko ◽  
Robert Shenkar ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Alveolar Macrophages ◽  
Distress Syndrome ◽  
Regulatory Mechanisms

scholarly journals Acute Respiratory Distress Syndrome is associated with impaired alveolar macrophage efferocytosis

2021 ◽  
Author(s):  
Rahul Y Mahida ◽  
Aaron Scott ◽  
Dhruv Parekh ◽  
Sebastian T Lugg ◽  
Rowan Hardy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Alveolar Macrophage ◽  
Clinical Outcomes ◽  
Alveolar Macrophages ◽  
Distress Syndrome ◽  
Receptor Expression ◽  
Neutrophil Apoptosis

Background: Alveolar macrophage dysfunction may contribute to Acute Respiratory Distress Syndrome (ARDS) pathogenesis, however this has been little studied. Objective: To investigate the pathophysiological link between alveolar macrophage efferocytosis, alveolar neutrophil apoptosis and clinical outcomes in ARDS patients, and to determine whether efferocytosis can be restored. Methods: Ventilated sepsis patients with or without ARDS underwent broncho-alveolar lavage. Apoptosis of alveolar neutrophils was assessed using flow cytometry. Alveolar macrophages were isolated and used in flow cytometric efferocytosis assays with labelled apoptotic neutrophils. Alveolar macrophages were also isolated from the lung tissue of lobectomy patients, then treated with pooled ARDS BAL fluid prior to functional assessment. Rac1 gene expression was assessed using RT-qPCR. Results: Patients with sepsis-related ARDS have decreased alveolar macrophage efferocytosis and increased alveolar neutrophil apoptosis compared to control ventilated sepsis patients. Across all ventilated sepsis patients, alveolar macrophage efferocytosis correlated negatively with alveolar cytokines (IL-8, IL-1ra), duration of ventilation and mortality. ARDS BAL treatment of alveolar macrophages decreased efferocytosis and Rac1 gene expression, however bacterial phagocytosis was preserved. Unexpectedly, alveolar macrophage efferocytosis receptor expression (MerTK, CD206) decreased and expression of the anti-efferocytosis receptor SIRPα increased following ARDS BAL treatment. Rho-associated kinase inhibition partially restored alveolar macrophage efferocytosis in an in vitro model of ARDS. Conclusions: Patients with sepsis-related ARDS have impaired alveolar macrophage efferocytosis, resulting in persistent inflammation from secondary neutrophil necrosis. This potentially has a negative effect on clinical outcomes, including mortality. Strategies to upregulate AM efferocytosis may be of value for attenuating inflammation in ARDS.

COVID-19 – eine vaskuläre Systemerkrankung

2020 ◽  
Vol 49 (10) ◽  
pp. 418-421
Author(s):  
Christopher Werlein ◽  
Peter Braubach ◽  
Vincent Schmidt ◽  
Nicolas J. Dickgreber ◽  
Bruno Märkl ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome

ZUSAMMENFASSUNGDie aktuelle COVID-19-Pandemie verzeichnet mittlerweile über 18 Millionen Erkrankte und 680 000 Todesfälle weltweit. Für die hohe Variabilität sowohl der Schweregrade des klinischen Verlaufs als auch der Organmanifestationen fanden sich zunächst keine pathophysiologisch zufriedenstellenden Erklärungen. Bei schweren Krankheitsverläufen steht in der Regel eine pulmonale Symptomatik im Vordergrund, meist unter dem Bild eines „acute respiratory distress syndrome“ (ARDS). Darüber hinaus zeigen sich jedoch in unterschiedlicher Häufigkeit Organmanifestationen in Haut, Herz, Nieren, Gehirn und anderen viszeralen Organen, die v. a. durch eine Perfusionsstörung durch direkte oder indirekte Gefäßwandschädigung zu erklären sind. Daher wird COVID-19 als vaskuläre Multisystemerkrankung aufgefasst. Vor dem Hintergrund der multiplen Organmanifestationen sind klinisch-pathologische Obduktionen eine wichtige Grundlage der Entschlüsselung der Pathomechanismen von COVID-19 und auch ein Instrument zur Generierung und Hinterfragung innovativer Therapieansätze.

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