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The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness

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dc.creator Gonzalo, José Ángel
dc.creator Lloyd, Clare M.
dc.creator Wen, Danyi
dc.creator Albar, Juan Pablo
dc.creator Wells, Timothy N.C.
dc.creator Proudfoot, Amanda
dc.creator Martínez-Alonso, Carlos
dc.creator Gutiérrez Ramos, José Carlos
dc.date 2008-04-17T08:54:53Z
dc.date 2008-04-17T08:54:53Z
dc.date 1998-07
dc.date.accessioned 2017-01-31T01:02:28Z
dc.date.available 2017-01-31T01:02:28Z
dc.identifier The Journal of Experimental Medicine, volume 188, number 1, July 6, 1998, pp. 157–167
dc.identifier 0022-1007
dc.identifier http://hdl.handle.net/10261/3634
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3634
dc.description Copyright by The Rockefeller University Press
dc.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 1 a , 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.
dc.description Peer reviewed
dc.format 3476434 bytes
dc.format application/pdf
dc.language eng
dc.publisher Rockefeller University Press
dc.rights openAccess
dc.subject Chemokines
dc.subject Allergic inflammation
dc.subject Bronchial hyperresponsiveness
dc.title The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness
dc.type Artículo


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