1. Impairment of Leukocyte Trafficking in a Murine Pleuritis Model by IL-4 and IL-10
- Author
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Fine, Jay S., Rojas-Triana, Alberto, Jackson, James V., Engstrom, Laura W., Deno, Gregory S., Lundell, Daniel J., and Bober, Loretta A.
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Cell migration -- Research ,Interleukins -- Properties ,Leukocytes -- Physiological aspects ,Health - Abstract
Byline: Jay S. Fine (1), Alberto Rojas-Triana (1), James V. Jackson (1), Laura W. Engstrom (1), Gregory S. Deno (1), Daniel J. Lundell (1), Loretta A. Bober (1) Keywords: chemokine; cytokine; leukocyte trafficking; pleuritis Abstract: 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-1[beta] and TNF[alpha] and the chemokines KC, MIP-2, CXCL9, CXCL10, CXCL11, CCL2, CCL3, and CCL4 at 6 h postchallenge, which diminished over time. In contrast, I3IFN 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 I3IFN 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 I3IFN, 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. Author Affiliation: (1) Department of Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey Article History: Registration Date: 20/10/2004
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- 2003