Impairment of leukocyte trafficking in a murine pleuritis model by IL-4 and IL-10

We have characterized leukocyte migration to the pleural cavity in a methylated-BSA (mBSA)-induced model of murine delayed-type hypersensitivity and evaluated the ability of IL-4 and IL-10 to modulate this response. Neutrophils, macrophages, T cells, and dendritic cells migrated to the pleural cavit...

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Bibliographic Details
Published in:	Inflammation Vol. 27; no. 4; pp. 161 - 174
Main Authors:	Fine, Jay S, Rojas-Triana, Alberto, Jackson, James V, Engstrom, Laura W, Deno, Gregory S, Lundell, Daniel J, Bober, Loretta A
Format:	Journal Article
Language:	English
Published:	United States Springer Nature B.V 01-08-2003
Subjects:	Animals Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - therapeutic use Cell Movement - immunology Disease Models, Animal Female Interferon-gamma - antagonists & inhibitors Interferon-gamma - biosynthesis Interleukin-10 - administration & dosage Interleukin-10 - therapeutic use Interleukin-4 - administration & dosage Interleukin-4 - therapeutic use Leukocytes - immunology Leukocytes - metabolism Leukocytes - pathology Mice Pleural Cavity - immunology Pleural Cavity - pathology Pleurisy - immunology Pleurisy - pathology Pleurisy - prevention & control Recombinant Proteins - administration & dosage Recombinant Proteins - therapeutic use Serum Albumin, Bovine - administration & dosage Serum Albumin, Bovine - immunology
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Summary:	We have characterized leukocyte migration to the pleural cavity in a methylated-BSA (mBSA)-induced model of murine delayed-type hypersensitivity and evaluated the ability of IL-4 and IL-10 to modulate this response. Neutrophils, macrophages, T cells, and dendritic cells migrated to the pleural cavity in a time-dependent fashion following direct intrapleural antigen challenge, with neutrophils comprising the majority of exudate leukocytes in the cavity within the first 24 h and the number of mononuclear cells increasing at later times. Real-time quantitative PCR analysis of infiltrating leukocytes revealed a marked elevation of steady-state mRNA levels of IL-1beta and TNFalpha and the chemokines KC, MIP-2, CXCL9, CXCL10, CXCL11, CCL2, CCL3, and CCL4 at 6 h postchallenge, which diminished over time. In contrast, gammaIFN mRNA levels were maximal at 24 h and CCL5 expression was sustained throughout 72 h. ELISA analysis of pleural exudate fluid revealed significant elevations of KC and CCL2 protein levels at 6 h postantigen challenge and a peak increase in gammaIFN protein at 24 h, confirming our mRNA observations. Administration of recombinant murine IL-4 or IL-10 prior to challenge significantly blocked cell trafficking to the pleural cavity as well as peak levels of exudate gammaIFN, with IL-4 being more potent in impairing these responses. IL-4 administration also increased the proportion of naive T cells in the pleural cavity, as judged by CD62L and CD45RB expression. These results indicate that this in vivo model demonstrates a pattern of events associated with Th1-mediated leukocyte trafficking and underscore the potential utility of this in vivo model for evaluating therapeutic inhibitors of leukocyte trafficking.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0360-3997 1573-2576
DOI:	10.1023/A:1025076111950