Transforming growth factor alpha binds to Trypanosoma cruzi amastigotes to induce signaling and cellular proliferation.

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. (125)I-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.