Cargando…
The Coordinated Action of CC Chemokines in the Lung Orchestrates Allergic Inflammation and Airway Hyperresponsiveness
The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated accumulation and activation of different leukocyte subsets in the lung. The development and maintenance of these processes correlate with the coordi...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1998
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525544/ https://www.ncbi.nlm.nih.gov/pubmed/9653092 |
_version_ | 1782158662985318400 |
---|---|
author | Gonzalo, Jose-Angel Lloyd, Clare M. Wen, Danyi Albar, Juan P. Wells, Timothy N.C. Proudfoot, Amanda Martinez-A, C. Dorf, Martin Bjerke, Torbjörn Coyle, Anthony J. Gutierrez-Ramos, Jose-Carlos |
author_facet | Gonzalo, Jose-Angel Lloyd, Clare M. Wen, Danyi Albar, Juan P. Wells, Timothy N.C. Proudfoot, Amanda Martinez-A, C. Dorf, Martin Bjerke, Torbjörn Coyle, Anthony J. Gutierrez-Ramos, Jose-Carlos |
author_sort | Gonzalo, Jose-Angel |
collection | PubMed |
description | The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated accumulation and activation of different leukocyte subsets in the lung. The development and maintenance of these processes correlate with the coordinated production of chemokines. Here, we have assessed the role that different chemokines play in lung allergic inflammation and BHR by blocking their activities in vivo. Our results show that blockage of each one of these chemokines reduces both lung leukocyte infiltration and BHR in a substantially different way. Thus, eotaxin neutralization reduces specifically BHR and lung eosinophilia transiently after each antigen exposure. Monocyte chemoattractant protein (MCP)-5 neutralization abolishes BHR not by affecting the accumulation of inflammatory leukocytes in the airways, but rather by altering the trafficking of the eosinophils and other leukocytes through the lung interstitium. Neutralization of RANTES (regulated upon activation, normal T cell expressed and secreted) receptor(s) with a receptor antagonist decreases significantly lymphocyte and eosinophil infiltration as well as mRNA expression of eotaxin and RANTES. In contrast, neutralization of one of the ligands for RANTES receptors, macrophage-inflammatory protein 1α, reduces only slightly lung eosinophilia and BHR. Finally, MCP-1 neutralization diminishes drastically BHR and inflammation, and this correlates with a pronounced decrease in monocyte- and lymphocyte-derived inflammatory mediators. These results suggest that different chemokines activate different cellular and molecular pathways that in a coordinated fashion contribute to the complex pathophysiology of asthma, and that their individual blockage results in intervention at different levels of these processes. |
format | Text |
id | pubmed-2525544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1998 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-25255442008-08-27 The Coordinated Action of CC Chemokines in the Lung Orchestrates Allergic Inflammation and Airway Hyperresponsiveness Gonzalo, Jose-Angel Lloyd, Clare M. Wen, Danyi Albar, Juan P. Wells, Timothy N.C. Proudfoot, Amanda Martinez-A, C. Dorf, Martin Bjerke, Torbjörn Coyle, Anthony J. Gutierrez-Ramos, Jose-Carlos J Exp Med Articles The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated accumulation and activation of different leukocyte subsets in the lung. The development and maintenance of these processes correlate with the coordinated production of chemokines. Here, we have assessed the role that different chemokines play in lung allergic inflammation and BHR by blocking their activities in vivo. Our results show that blockage of each one of these chemokines reduces both lung leukocyte infiltration and BHR in a substantially different way. Thus, eotaxin neutralization reduces specifically BHR and lung eosinophilia transiently after each antigen exposure. Monocyte chemoattractant protein (MCP)-5 neutralization abolishes BHR not by affecting the accumulation of inflammatory leukocytes in the airways, but rather by altering the trafficking of the eosinophils and other leukocytes through the lung interstitium. Neutralization of RANTES (regulated upon activation, normal T cell expressed and secreted) receptor(s) with a receptor antagonist decreases significantly lymphocyte and eosinophil infiltration as well as mRNA expression of eotaxin and RANTES. In contrast, neutralization of one of the ligands for RANTES receptors, macrophage-inflammatory protein 1α, reduces only slightly lung eosinophilia and BHR. Finally, MCP-1 neutralization diminishes drastically BHR and inflammation, and this correlates with a pronounced decrease in monocyte- and lymphocyte-derived inflammatory mediators. These results suggest that different chemokines activate different cellular and molecular pathways that in a coordinated fashion contribute to the complex pathophysiology of asthma, and that their individual blockage results in intervention at different levels of these processes. The Rockefeller University Press 1998-07-01 /pmc/articles/PMC2525544/ /pubmed/9653092 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Gonzalo, Jose-Angel Lloyd, Clare M. Wen, Danyi Albar, Juan P. Wells, Timothy N.C. Proudfoot, Amanda Martinez-A, C. Dorf, Martin Bjerke, Torbjörn Coyle, Anthony J. Gutierrez-Ramos, Jose-Carlos The Coordinated Action of CC Chemokines in the Lung Orchestrates Allergic Inflammation and Airway Hyperresponsiveness |
title | The Coordinated Action of CC Chemokines in the
Lung Orchestrates Allergic Inflammation and
Airway Hyperresponsiveness
|
title_full | The Coordinated Action of CC Chemokines in the
Lung Orchestrates Allergic Inflammation and
Airway Hyperresponsiveness
|
title_fullStr | The Coordinated Action of CC Chemokines in the
Lung Orchestrates Allergic Inflammation and
Airway Hyperresponsiveness
|
title_full_unstemmed | The Coordinated Action of CC Chemokines in the
Lung Orchestrates Allergic Inflammation and
Airway Hyperresponsiveness
|
title_short | The Coordinated Action of CC Chemokines in the
Lung Orchestrates Allergic Inflammation and
Airway Hyperresponsiveness
|
title_sort | coordinated action of cc chemokines in the
lung orchestrates allergic inflammation and
airway hyperresponsiveness |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525544/ https://www.ncbi.nlm.nih.gov/pubmed/9653092 |
work_keys_str_mv | AT gonzalojoseangel thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT lloydclarem thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT wendanyi thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT albarjuanp thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT wellstimothync thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT proudfootamanda thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT martinezac thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT dorfmartin thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT bjerketorbjorn thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT coyleanthonyj thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT gutierrezramosjosecarlos thecoordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT gonzalojoseangel coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT lloydclarem coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT wendanyi coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT albarjuanp coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT wellstimothync coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT proudfootamanda coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT martinezac coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT dorfmartin coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT bjerketorbjorn coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT coyleanthonyj coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness AT gutierrezramosjosecarlos coordinatedactionofccchemokinesinthelungorchestratesallergicinflammationandairwayhyperresponsiveness |