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Infection and Immunity, November 2000, p. 6355-6361, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Essential Role of Platelet-Activating Factor in Control of Leishmania (Leishmania) amazonensis Infection

Maria Valdrinez Campana Lonardoni,1 Momtchillo Russo,2 and Sonia Jancar2,*

Department of Clinical Analyses, State University of Maringá, Maringá, Paraná,1 and Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo,2 Brazil

Received 13 April 2000/Returned for modification 5 June 2000/Accepted 1 August 2000

In the present study we investigated the role of platelet-activating factor (PAF) and prostaglandins in experimental Leishmania (Leishmania) amazonensis infection and the relationship between these mediators and nitric oxide (NO) production. Mouse peritoneal macrophages elicited with thioglicolate were infected with leishmania amastigotes, and the infection index determined 48 h later. The course of infection was monitored for 5 weeks in mice infected in the footpad with promastigotes by measuring the footpad swelling and parasite load in regional lymph nodes and spleen. The addition of PAF to C57BL/6 mouse macrophages significantly inhibited parasite growth and induced NO production. Treatment of macrophages with a selective PAF antagonist, WEB2086, increased the infection, indicating that endogenously produced PAF regulates macrophage ability to control leishmania infection. This effect of PAF was abolished by addition of the inhibitor of NO synthesis, L-NAME, to the cultures. The addition of prostaglandin E2 significantly increased the infection and NO production. Treatment with cyclo-oxygenase inhibitor, indomethacin, reduced the infection and PAF-induced release of NO. Thus, the increased NO production induced by PAF seems to be mediated by prostaglandins. The more-selective inhibitors of cyclo-oxygenase 2, nimesulide and NS-398, had no significant effect. Thus, antileishmanial activity correlates better with the presence of PAF or absence of prostaglandins than with NO production. In vivo treatment with PAF antagonists significantly increased leishmania lesions, as well as the parasite load, in regional lymph nodes and spleens. These findings indicate that PAF is essential for the control of leishmania infection.

* Corresponding author. Mailing address: Department of Immunology, ICB/USP, Av. Prof. Lineu Prestes, 1730, CEP 05508-900, São Paulo, SP, Brazil. Phone: 55-11-3818-7393. Fax: 55-11-3818-7224. E-mail: sojancar{at}icb.usp.br.

Infection and Immunity, November 2000, p. 6355-6361, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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