THE EFFECT OF FETUIN AND OTHER SIALOGLYCOPROTEINS ON THE INVITRO PENETRATION OF TRYPANOSOMA-CRUZI TRYPOMASTIGOTES INTO FIBROBLASTIC CELLS

Heat-inactivated calf-, human-, and especially fetal calf serum stimulate infection of Vero cells by cell culture-derived trypomastigotes of Trypanosoma cruzi: the stimulatory effect is more marked with extracellular activated parasites or trypsinized trypomastigotes than with recently released parasites. The augmented invasion is not the consequence of a stimulation of attachment of trypomastigotes to host cells. Various sialoglycoproteins like fetuin, transferrin, fibrinogen, .alpha.-1-antitrypsin, mucin and goat-IgG are also effective in enhancing in vitro infectivity. Colominic acid also stimulates invasion, but other non-sialic polyanionic compounds are either ineffective (chondroitin sulfate, poly-aspartic acid) or inhibitory (heparin, phytic acid, myo-inositol hexasulfate). Fetuin, the best stimulatory compound tested, gives half-maximal activation with approximately 0.03 mg ml-1, and total activation with 0.5-1 mg ml-1. The enhancement of infectivity is time-dependent (2-3 h for maximal activation) at 37.degree. C and does not occur at 0.degree. C. Desialidated-fetuin or -fetal calf serum do not stimulate infectivity at all. Treatment with fetuin of parasites alone (or Vero cells alone), followed by removal of free fetuin and by interaction with untreated Vero cells (or parasites) indicates that the stimulation effect of fetuin occurs mainly on the trypomastigotes. No specific binding of [125I]fetuin to the parasites could be demonstrated, and incubation with exogenous neuraminidase of trypomastigotes previously activated by fetuin, reverses nearly completely the stimulation. Since a transfer of sialyl residues from exogenous sialoconjugates to epimastigotes has been recently reported [Previato eta l. (1985) Mol. Biochem. Parasitol. 16, 85-96] and the behaviour of the stimulation by sialoglycoproteins of trypomastigote infectivity is compatible with such an enzymatic reaction, the hypothesis is here advanced that sialylation of T. cruzi surface components is involved in the invasion of fibroblastic cells by cell culture-derived trypomastigotes.