Eosinophil Recruitment in Type-2 Hypersensitivity Pulmonary Granulomas

Autor: Bo Chin Chiu, Steven L. Kunkel, Valerie R. Stolberg, Xiao Zhou Shang, Nicholas W. Lukacs, Stephen W. Chensue, Hedwig S. Murphy
Rok vydání: 2002
Předmět:
Zdroj: The American Journal of Pathology. 161:257-266
ISSN: 0002-9440
DOI: 10.1016/s0002-9440(10)64177-6
Popis: Monocyte chemotactic protein-3 (MCP-3/CCL7) has potent eosinophil chemoattractant properties. The present study determined its relative contribution to the formation of Th2 cytokine-mediated (type-2) eosinophil-rich interstitial lung granulomas induced by antigens of Schistosoma mansoni eggs. Both MCP-3 transcripts and protein levels were more strongly expressed in lungs with type-2 than with type-1 (mycobacterial antigen-elicited Th1-mediated) granulomas. In vivo treatment with neutralizing antibodies demonstrated that MCP-3 abrogated eosinophil accumulation in type-2 lesions by 40 to 50%. Immunohistochemical staining revealed that MCP-3 localized to vessels in or near granulomas suggesting that endothelial cells were an important in situ source of MCP-3. Maximal MCP-3 transcript expression was abrogated by anti-interleukin-4 treatment. Furthermore, cultured mouse lung endothelial cells displayed augmented MCP-3 production in response to interleukin-4. Together, these results suggest that MCP-3 contributes to a significant component of eosinophil recruitment in the type-2 interstitial granuloma formation and Th2 cytokines promote its production.
Databáze: OpenAIRE