title: Alveolar macrophages initiate the systemic microvascular inflammatory response to alveolar hypoxia.
abstract: Alveolar hypoxia occurs as a result of a decrease in the environmental [Formula: see text] , as in altitude, or in clinical conditions associated with a global or regional decrease in alveolar ventilation. Systemic effects, in most of which an inflammatory component has been identified, frequently accompany both acute and chronic forms of alveolar hypoxia. Experimentally, it has been shown that acute exposure to environmental hypoxia causes a widespread systemic inflammatory response in rats and mice. Recent research has demonstrated that alveolar macrophages, in addition to their well known intrapulmonary functions, have systemic, extrapulmonary effects when activated, and indirect evidence suggest these cells may play a role in the systemic consequences of alveolar hypoxia. This article reviews studies showing that the systemic inflammation of acute alveolar hypoxia observed in rats is not initiated by the low systemic tissue [Formula: see text] , but rather by a chemokine, Monocyte Chemoattractant Protein-1 (MCP-1, or CCL2) released by alveolar macrophages stimulated by hypoxia and transported by the circulation. Circulating MCP-1, in turn, activates perivascular mast cells to initiate the microvascular inflammatory cascade. The research reviewed here highlights the extrapulmonary effects of alveolar macrophages and provides a possible mechanism for some of the systemic effects of alveolar hypoxia.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Chao
authors.forename: John G
authors.initials: JG
authors.lastname: Wood
authors.forename: Norberto C
authors.initials: NC
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D055806:Microvessels / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology
chemical_list: D018932:Chemokine CCL2