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

Dexamethasone blocks the systemic inflammation of alveolar hypoxia at several sites in the... 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 P o 2 . 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% O 2 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. alveolar macrophages mast cells Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print May 18, 2012 , doi: 10.​1152/​ajpheart.​00106.​2012 AJP - Heart July 15, 2012 vol. 303 no. 2 H168-H177 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpheart.00106.2012v1 303/2/H168 most recent Classifications Vascular Biology and Microcirculation Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Chao, J. Articles by Gonzalez, N. C. PubMed PubMed citation Articles by Chao, J. Articles by Gonzalez, N. C. Related Content Vascular Biology and Microcirculation Load related web page information Current Content July 15, 2012 Alert me to new issues of AJP - Heart About the Journal Calls for Papers Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6135 Online ISSN: 1522-1539 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview(); } catch(err) {} var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-189672-30"); pageTracker._setDomainName(".physiology.org"); pageTracker._trackPageview(); } catch(err) {} http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Heart and Circulatory Physiology The American Physiological Society

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

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References (46)

Publisher
The American Physiological Society
Copyright
Copyright © 2012 the American Physiological Society
ISSN
0363-6135
eISSN
1522-1539
DOI
10.1152/ajpheart.00106.2012
pmid
22610172
Publisher site
See Article on Publisher Site

Abstract

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 P o 2 . 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% O 2 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. alveolar macrophages mast cells Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print May 18, 2012 , doi: 10.​1152/​ajpheart.​00106.​2012 AJP - Heart July 15, 2012 vol. 303 no. 2 H168-H177 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpheart.00106.2012v1 303/2/H168 most recent Classifications Vascular Biology and Microcirculation Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Chao, J. Articles by Gonzalez, N. C. PubMed PubMed citation Articles by Chao, J. Articles by Gonzalez, N. C. Related Content Vascular Biology and Microcirculation Load related web page information Current Content July 15, 2012 Alert me to new issues of AJP - Heart About the Journal Calls for Papers Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6135 Online ISSN: 1522-1539 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview(); } catch(err) {} var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-189672-30"); pageTracker._setDomainName(".physiology.org"); pageTracker._trackPageview(); } catch(err) {}

Journal

AJP - Heart and Circulatory PhysiologyThe American Physiological Society

Published: Jul 15, 2012

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