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Glycosylphosphatidylinositol‐anchored mucin‐like glycoproteins isolated from Trypanosoma cruzi trypomastigotes induce in vivo leukocyte recruitment dependent on MCP‐1 production by IFN‐γ‐primed‐macrophages
Author(s) -
Coelho Patrícia S.,
Klein André,
Talvani André,
Coutinho Sibele F.,
Takeuchi Osamu,
Akira Shizuo,
Silva João S.,
Canizzaro Hélia,
Gazzinelli Ricardo T.,
Teixeira Mauro M.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.71.5.837
Subject(s) - mucin , biology , chemokine , trypanosoma cruzi , in vivo , proinflammatory cytokine , immunology , immune system , inflammation , microbiology and biotechnology , biochemistry , parasite hosting , world wide web , computer science
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‐γ‐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‐1α 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‐γ. 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‐γ may drive tissue chemokine production and inflammation and bear a significant role in the pathogenesis of Chagas disease.