scholarly journals Alveolar Hypoxia-Induced Pulmonary Inflammation: From Local Initiation to Secondary Promotion by Activated Systemic Inflammation

2016 ◽  
Vol 53 (5-6) ◽  
pp. 317-329 ◽  
Author(s):  
Ting Chen ◽  
Chengzhong Yang ◽  
Manman Li ◽  
Xiaoling Tan
Keyword(s):  
Systemic Inflammation ◽  
Pulmonary Inflammation ◽  
Alveolar Hypoxia

scholarly journals Impaired hypoxic pulmonary vasoconstriction in a mouse model of Leigh syndrome

2019 ◽  
Vol 316 (2) ◽  
pp. L391-L399 ◽  
Author(s):  
Grigorij Schleifer ◽  
Eizo Marutani ◽  
Michele Ferrari ◽  
Rohit Sharma ◽  
Owen Skinner ◽  
...  
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Inflammation ◽  
Leigh Syndrome ◽  
Arterial Oxygen ◽  
Inborn Errors ◽  
Pulmonary Vasoconstriction ◽  
Progressive Encephalopathy ◽  
Alveolar Hypoxia ◽  
The Impact ◽  
Deficient Mice

Hypoxic pulmonary vasoconstriction (HPV) is a physiological vasomotor response that maintains systemic oxygenation by matching perfusion to ventilation during alveolar hypoxia. Although mitochondria appear to play an essential role in HPV, the impact of mitochondrial dysfunction on HPV remains incompletely defined. Mice lacking the mitochondrial complex I (CI) subunit Ndufs4 ( Ndufs4−/−) develop a fatal progressive encephalopathy and serve as a model for Leigh syndrome, the most common mitochondrial disease in children. Breathing normobaric 11% O2 prevents neurological disease and improves survival in Ndufs4−/− mice. In this study, we found that either genetic Ndufs4 deficiency or pharmacological inhibition of CI using piericidin A impaired the ability of left mainstem bronchus occlusion (LMBO) to induce HPV. In mice breathing air, the partial pressure of arterial oxygen during LMBO was lower in Ndufs4−/− and in piericidin A-treated Ndufs4+/+ mice than in respective controls. Impairment of HPV in Ndufs4−/− mice was not a result of nonspecific dysfunction of the pulmonary vascular contractile apparatus or pulmonary inflammation. In Ndufs4-deficient mice, 3 wk of breathing 11% O2 restored HPV in response to LMBO. When compared with Ndufs4−/− mice breathing air, chronic hypoxia improved systemic oxygenation during LMBO. The results of this study show that, when breathing air, mice with a congenital Ndufs4 deficiency or chemically inhibited CI function have impaired HPV. Our study raises the possibility that patients with inborn errors of mitochondrial function may also have defects in HPV.

scholarly journals Alveolar hypoxia, alveolar macrophages, and systemic inflammation

2009 ◽  
Vol 10 (1) ◽  
Author(s):  
Jie Chao ◽  
John G Wood ◽  
Norberto C Gonzalez
Keyword(s):  
Systemic Inflammation ◽  
Alveolar Macrophages ◽  
Alveolar Hypoxia

scholarly journals Alveolar macrophages participate in the systemic inflammation of alveolar hypoxia

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Norberto C. Gonzalez ◽  
Gustavo Blanco ◽  
Eric Schmidt ◽  
Julie Allen ◽  
John Wood
Keyword(s):  
Systemic Inflammation ◽  
Alveolar Macrophages ◽  
Alveolar Hypoxia

scholarly journals Dexamethasone blocks the systemic inflammation of alveolar hypoxia at several sites in the inflammatory cascade

2012 ◽  
Vol 303 (2) ◽  
pp. H168-H177 ◽  
Author(s):  
Jie Chao ◽  
Zachary Viets ◽  
Paula Donham ◽  
John G. Wood ◽  
Norberto C. Gonzalez
Keyword(s):  
Systemic Inflammation ◽  
Primary Cultures ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Monocyte Chemoattractant Protein 1 ◽  
Inflammatory Cascade ◽  
Monocyte Chemoattractant ◽  
Alveolar Hypoxia ◽  
Key Steps

Alveolar hypoxia produces a rapid and widespread systemic inflammation in rats. The inflammation is initiated by the release into the circulation of monocyte chemoattractant protein-1 (MCP-1) from alveolar macrophages (AMO) activated by the low alveolar Po2. Circulating MCP-1 induces mast cell (MC) degranulation with renin release and activation of the local renin-angiotensin system, leading to microvascular leukocyte recruitment and increased vascular permeability. We investigated the effect of dexamethasone, a synthetic anti-inflammatory glucocorticoid, on the development of the systemic inflammation of alveolar hypoxia and its site(s) of action in the inflammatory cascade. The inflammatory steps investigated were the activation of primary cultures of AMO by hypoxia, the degranulation of MCs by MCP-1 in the mesentery microcirculation of rats, and the effect of angiotensin II (ANG II) on the leukocyte/endothelial interface of the mesentery microcirculation. Dexamethasone prevented the mesentery inflammation in conscious rats breathing 10% O2 for 4 h by acting in all key steps of the inflammatory cascade. Dexamethasone: 1) blocked the hypoxia-induced AMO activation and the release of MCP-1 and abolished the increase in plasma MCP-1 of conscious, hypoxic rats; 2) prevented the MCP-1-induced degranulation of mesentery perivascular MCs and reduced the number of peritoneal MCs, and 3) blocked the leukocyte-endothelial adherence and the extravasation of albumin induced by topical ANG II in the mesentery. The effect at each site was sufficient to prevent the AMO-initiated inflammation of hypoxia. These results may explain the effectiveness of dexamethasone in the treatment of the systemic effects of alveolar hypoxia.

scholarly journals Renin from activated mast cells mediates the systemic inflammation of alveolar hypoxia

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Jie Chao ◽  
V Gustavo Blanco ◽  
John G. Wood ◽  
Norberto C. Gonzalez
Keyword(s):  
Mast Cells ◽  
Systemic Inflammation ◽  
Alveolar Hypoxia
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