title: Alveolar Hypoxia-Induced Pulmonary Inflammation: From Local Initiation to Secondary Promotion by Activated Systemic Inflammation.
abstract: Pulmonary hypertension (PH) is a pathological condition with high mortality and morbidity. Hypoxic PH (HPH) is a common form of PH occurring mainly due to lung disease and/or hypoxia. Most causes of HPH are associated with persistent or intermittent alveolar hypoxia, including exposure to high altitude and chronic obstructive respiratory disease. Recent evidence suggests that inflammation is a critical step for HPH initiation and development. A detailed understanding of the initiation and progression of pulmonary inflammation would help in exploring potential clinical treatments for HPH. In this review, the mechanism for alveolar hypoxia-induced local lung inflammation and its progression are discussed as follows: (1) low alveolar PO2 levels activate resident lung cells, mainly the alveolar macrophages, which initiate pulmonary inflammation; (2) systemic inflammation is induced by alveolar hypoxia through alveolar macrophage activation; (3) monocytes are recruited into the pulmonary circulation by alveolar hypoxia-induced macrophage activation, which then contributes to the progression of pulmonary inflammation during the chronic phase of alveolar hypoxia, and (4) alveolar hypoxia-induced systemic inflammation contributes to the development of HPH. We hypothesize that a combination of alveolar hypoxia-induced local lung inflammation and the initiation of systemic inflammation ("second hit") is essential for HPH progression.
authors.affiliation: Department of High Altitude Physiology and Biology, College of High Altitude Medicine, Third Military Medical University, Ministry of Education, Chongqing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.forename: Chengzhong
authors.initials: C
authors.lastname: Yang
authors.forename: Manman
authors.initials: M
authors.lastname: Li
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Tan
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte; D018450:Disease Progression; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000503:physiopathology; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators; D010100:Oxygen