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(Journal of Leukocyte Biology. 2002;72:1215-1227.)
© 2002 by Society for Leukocyte Biology

Identification and characterization of a novel mouse gene encoding a Ras-associated guanine nucleotide exchange factor: expression in macrophages and myocarditis elicited by Trypanosoma cruzi parasites

Ludmila R. P. Ferreira^*,,, Eduardo F. Abrantes, Cibele V. Rodrigues^*, Braulia Caetano^*,, Gustavo C. Cerqueira^*, Anna Christina Salim, Luiz F. L. Reis and Ricardo T. Gazzinelli^*,

^* Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil;
Centro de Pesquisas René Rachou, Oswaldo Cruz Foundation, Belo Horizonte, MG, Brazil; and
Ludwig Institute for Cancer Research, São Paulo, SP, Brazil

Correspondence: Dr. Ricardo T. Gazzinelli, Laboratory of Immunopathology, Centro de Pesquisas René Rachou, FIOCRUZ, Av. Augusto de Lima 1715, 30190-002 Belo Horizonte, MG, Brazil. E-mail: ritoga{at}dedalus.lcc.ufmg.br

The ability of Trypanosoma cruzi to activate macrophages is, at least in part, attributed to the glycosylphosphatidylinositol-anchored mucin-like glycoproteins (GPI-mucins) expressed in the surface of the trypomastigote stage of the parasite. The differential display reverse transcriptase-polymerase chain reaction and the reverse Northern blot were used to study modulation of gene expression in murine macrophages exposed to GPI-mucins and in cardiac tissues from mice infected with T. cruzi. Among several cDNAs that were more abundant in lanes corresponding to macrophages stimulated with GPI-mucins as compared with resting cells, we confirmed the differential expression of A1, interleukin-18, and GPI4. Some of these genes were also shown to have enhanced expression in the cardiac tissue (DAP-12, A1, and GPI4) from infected animals. The expression of GPI4 was also enhanced in human monocytes stimulated with GPI-mucins or bacterial lipopolysaccharides. The complete sequence of the GPI4 transcript and its gene including the 5' upstream region was defined. GPI4 was encoded by a novel, single copy gene present in mouse as well as human genomes and showed conserved homology to different members of the guanine nucleotide exchange factor family.

Key Words: GPI-mucins • NF-B • Ras-GEF • Toll-like receptors

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