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Infection and Immunity, July 2003, p. 4201-4205, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.4201-4205.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Transforming Growth Factor {alpha} Binds to Trypanosoma cruzi Amastigotes To Induce Signaling and Cellular Proliferation

A. Deloris Alexander,{dagger} Fernando Villalta, and Maria F. Lima*

Department of Microbiology, Meharry Medical College, Nashville, Tennessee 37208

Received 27 November 2002/ Returned for modification 1 April 2003/ Accepted 14 April 2003

Macrophages secrete transforming growth factor {alpha} (TGF-{alpha}) to trigger proliferation of cancer cells. Here, we report a new role for TGF-{alpha} in modulating the direct cellular proliferation of a parasitic protozoan, Trypanosoma cruzi. Amastigotes present two classes of receptors for TGF-{alpha} with different binding affinities. 125I-TGF-{alpha} binding was competed by an excess of cold epidermal growth factor and TGF-{alpha} but not by an irrelevant molecule. Upon binding of TGF-{alpha} to amastigotes, the ligand is internalized, inducing trypanosome tyrosine phosphorylation of 90- and 87-kDa proteins and increasing DNA synthesis and proliferation of amastigotes. Furthermore, exposure of macrophages to TGF-{alpha} induced increased amastigote proliferation. These results describe a novel mechanism used by amastigotes to regulate their proliferation mediated by a TGF-{alpha}-dependent signal transduction pathway.


* Corresponding author. Mailing address: Department of Microbiology, Meharry Medical College, Nashville, TN 37208. Phone: (615) 327-6533. Fax: (615) 327-6535. E-mail: mflima{at}mail.mmc.edu.

Editor: J. M. Mansfield

{dagger} Present address: Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, Chapel Hill, NC 27514.


Infection and Immunity, July 2003, p. 4201-4205, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.4201-4205.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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