| Alveolar hypoxia-induced systemic inflammation: what low PO(2) does and does not do. | |
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MedLine Citation:
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PMID: 20204767 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Reduction of alveolar PO(2) (alveolar hypoxia, AH) may occur in pulmonary diseases such as chronic obstructive pulmonary disease (COPD), or in healthy individuals ascending to altitude. Altitude illnesses may develop in non-acclimatized persons who ascend rapidly. The mechanisms underlying these illnesses are not well understood, and systemic inflammation has been suggested as a possible contributor. Similarly, there is evidence of systemic inflammation in the systemic alterations present in COPD patients, although its role as a causative factor is not clear.We have observed that AH, induced by breathing 10% O(2) produces a rapid (minutes) and widespread micro vascular inflammation in rats and mice. This inflammation has been observed directly in the mesenteric, skeletal muscle, and pial microcirculations. The inflammation is characterized by mast cell degranulation, generation of reactive O(2) species, reduced nitric oxide levels, increased leukocyte-endothelial adherence in post-capillary venules, and extravasation of albumin. Activated mast cells stimulate the renin-angiotensin system (RAS) which leads to the inflammatory response via activation of NADPH oxidase. If the animals remain in hypoxia for several days, the inflammation resolves and exposure to lower PO(2) does not elicit further inflammation, suggesting that the vascular endothelium has "acclimatized" to hypoxia.Recent experiments in cremaster microcirculation suggest that the initial trigger of the inflammation is not the reduced tissue PO(2), but rather an intermediary released by alveolar macrophages into the circulation. The putative intermediary activates mast cells, which, in turn, stimulate the local renin-angiotensin system and induce inflammation. |
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Authors:
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Norberto C Gonzalez; John G Wood |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review |
Journal Detail:
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Title: Advances in experimental medicine and biology Volume: 662 ISSN: 0065-2598 ISO Abbreviation: Adv. Exp. Med. Biol. Publication Date: 2010 |
Date Detail:
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Created Date: 2010-03-05 Completed Date: 2010-03-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0121103 Medline TA: Adv Exp Med Biol Country: United States |
Other Details:
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Languages: eng Pagination: 27-32 Citation Subset: IM |
Affiliation:
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Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. ngonzale@kumc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Hypoxia Humans Inflammation / blood, pathology* Oxygen / pharmacology* Partial Pressure Pulmonary Alveoli / drug effects*, pathology* Renin-Angiotensin System / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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HL39443/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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