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Infection and Immunity, June 1999, p. 2810-2814, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Platelet-Activating Factor Induces Nitric Oxide Synthesis in Trypanosoma cruzi-Infected Macrophages and Mediates Resistance to Parasite Infection in Mice

Júlio C. S. Aliberti,1 Fabiana S. Machado,1 Ricardo T. Gazzinelli,2 Mauro M. Teixeira,3 and João S. Silva1,*

Department of Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo,1 and Department of Biochemistry and Immunology2 and Department of Pharmacology,3 ICB, UFMG, Belo Horizonte, Minas Gerais, Brazil

Received 22 January 1999/Accepted 4 March 1999

Trypanosoma cruzi replicates in nucleated cells and is susceptible to being killed by gamma interferon-activated macrophages through a mechanism dependent upon NO biosynthesis. In the present study, the role of platelet-activating factor (PAF) in the induction of NO synthesis and in the activation of the trypanocidal activity of macrophages was investigated. In vitro, PAF induced NO secretion by T. cruzi-infected macrophages and the secreted NO inhibited intracellular parasite growth. The addition of a PAF antagonist, WEB 2170, inhibited both NO biosynthesis and trypanocidal activity. The inducible NO synthase/L-arginine pathway mediated trypanocidal activity, since it was inhibited by treatment with L-N-monomethyl arginine (L-NMMA), an L-arginine analog. PAF-mediated NO production in infected macrophages appears to be dependent on tumor necrosis alpha (TNF-alpha ) production, since the addition of a neutralizing anti-TNF-alpha monoclonal antibody mAb inhibited NO synthesis. To test the role of PAF in mediating resistance or susceptibility to T. cruzi infection, infected mice were treated with WEB 2170, a PAF antagonist. These animals had higher parasitemia and earlier mortality than did vehicle-treated mice. Taken together, our results suggest that PAF belongs to a group of mediators that coordinate the mechanisms of resistance to infections with intracellular parasites.

* Corresponding author. Mailing address: Department of Immunology, FMRP/USP, Ribeirão Preto---SP 14049-900, Brazil. Phone: 55-16-602-3234. Fax: 55-16-633-6631. E-mail: jsdsilva{at}fmrp.usp.br.

Infection and Immunity, June 1999, p. 2810-2814, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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