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(Journal of Leukocyte Biology. 2002;71:837-844.)
© 2002 by Society for Leukocyte Biology

Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes induce in vivo leukocyte recruitment dependent on MCP-1 production by IFN--primed-macrophages

Patrícia S. Coelho^*, André Klein^*, André Talvani^*, Sibele F. Coutinho^*, Osamu Takeuchi, Shizuo Akira, João S. Silva, Hélia Canizzaro^*, Ricardo T. Gazzinelli^*, and Mauro M. Teixeira^*

^* Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan;
Departamento de Imunologia, Universidade de São Paulo, Ribeirão Preto, Brazil; and
Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil

Correspondence: Dr. Mauro M. Teixeira, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627–Pampulha, 31270-901 Belo Horizonte, MG, Brazil. E-mail: mmtex{at}icb.ufmg.br

Glycosylphosphatidylinositol-anchoredmucin-like glycoproteins from Trypanosoma cruzi trypomastigotes (tGPI-mucins) activate macrophages in vitro to produce proinflammatory cytokines, chemokines, and nitric oxide. These effects of tGPI-mucins may be important in the ensuing immune response to T. cruzi. Here, we have sought evidence for a role of tGPI-mucins in mediating leukocyte recruitment in vivo. tGPI-mucins are highly effective in promoting cell recruitment in the pleural cavity of mice primed with IFN--inducing agents but not in naïve mice. Maximal recruitment was observed at a dose between 250 and 1250 ng tGPI-mucins. There was a significant elevation in the levels of MCP-1 in the pleural cavity of primed animals injected with tGPI-mucins, and in vivo neutralization of MCP-1 abolished leukocyte recruitment. Pretreatment with anti-MIP-1 or anti-RANTES had no effect on the recruitment induced by tGPI-mucins. MCP-1 immunoreactivity was detected in pleural macrophages, and macrophages produced MCP-1 in vitro, especially after priming with IFN-. Finally, tGPI-mucins induced significant leukocyte recruitment in primed C3H/HeJ but not in TLR2-deficient mice. Together, our results suggest that T. cruzi-derived GPI-mucins in conjunction with IFN- may drive tissue chemokine production and inflammation and bear a significant role in the pathogenesis of Chagas disease.

Key Words: cell trafficking • inflammation • inflammatory mediators • chemokines • protozoan parasites

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