Effect of Platelet-Activating Factor on Cell Differentiation of Trypanosoma cruzi Claudia O. Rodrigues,* Patrícia M. L. Dutra,* Thais Souto-Padrón,² Renato S. B. Cordeiro,‡ and Angela H. C. S. Lopes* ,1,2 *Instituto de Microbiologia, and ²Instituto de Biofı ´sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil; and ‡Departamento de Fisiologia e Farmacodina ˆmica, Fundac ¸ão Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil Received May 6, 1996 The effects of platelet-activating factor (PAF), at 10 -6 M and 10 -9 M, on cell growth and cell differentiation of Trypanosoma cruzi were investigated. Cell differentiation was evaluated by both light and electron micros- copy. At the concentrations used, PAF slightly interfered with the protozoan growth. However, parasites growth in the presence of PAF were significantly more differentiated than those grown in the absence of PAF, beginning on the fourth day of culture. A specific PAF receptor antagonist (WEB 2086) totally abrogated PAF effect on cell differentiation. These findings indicate that PAF triggers the process of cell differentiation in T. cruzi and suggest that these parasites have receptors for PAF. © 1996 Academic Press, Inc. Trypanosoma cruzi, as well as other species of the family Trypanosomatidae, is a protozoan parasite which undergoes a process of cell differentiation. In this process one developmental stage transforms into another. The life cycle of T. cruzi, the etiologic agent of Chagas’ disease, comprises three distinct morphological stages (1). In the insect vector, the replicative epimastigote transforms into the metacyclic trypomastigote, which is infectious for mammalian cells. In these cells, trypo- mastigotes differentiate to amastigotes, which proliferate and turn again into trypomastigotes (2). The transformation of epimastigotes into metacyclic trypomastigotes (metacyclogenesis) is a crucial step during the life cycle of Trypanosoma cruzi. In addition to morphological changes, this process involves differential gene expression (3), changes in fatty acid composition and in cell- surface carbohydrates (4). The study of in vitro differentiation of T. cruzi was made possible by the establishment of a chemically defined medium (5). Platelet-activating factor (PAF-acether) is a potent lipid autacoid which exerts a wide range of biological activities, including cellular differentiation, inflammation and allergy (6). This factor is involved in various pathologies such as bronchial asthma, endotoxin shock and other disorders (7). PAF-acether is a substance formed and released from a variety of stimulated cells including platelets, neutrophils, macrophages, basophils, eosinophils and endothelial cells (8). All biological actions of PAF-acether seem to be mediated by specific membrane receptors (9). The use of receptor antagonists of PAF-acether has been proven to be a powerful tool for studies of PAF membrane receptors (7). In the present work we have studied the influence of PAF on the process of metacyclogenesis of T. cruzi, using Dm 28C clone, under chemically defined conditions (5). PAF-acether signifi- cantly increased the percentage of the most differentiated form (trypomastigote) of T. cruzi and the 1 This work was supported by FINEP, CNPq, CEPG-UFRJ and CAPES 2 To whom correspondence should be addressed. Fax #270-8793; email:immgahc@microbio.ufrj.br Abbreviations: PAF, platelet-activating factor; BHI, brain heart infusion; TAUP, triatomine artificial urine medium, supplemented with proline. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 223, 735–740 (1996) ARTICLE NO. 0965 735 0006-291X/96 $18.00 Copyright © 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.