The effect of swainsonine on the association of Trypanosoma cruzi with host cells.
The role of glycoprotein processing in Trypanosoma cruzi association with mammalian host cells (i.e., surface binding and internalization) was studied by using swainsonine - an inhibitor of glycoprotein processing. The presence of swainsonine in co-cultures of blood forms of T. cruzi with either mouse peritoneal macrophages or rat heart myoblasts markedly reduced parasite-host cell association as evidenced by significant decreases in both the percentage of cells associating with the organisms and the number of parasites per cell. This inhibition appeared to result from effects on both the parasite and the host cells since pretreatment of either one reduced its association with the untreated counterpart. The inhibitory effect of swainsonine on the host cells was demonstrable with trypomastigote forms derived from either infected mouse blood or the feces of infected insect vectors, and also with amastigotes. Conversely, treatment of the parasites with swainsonine inhibited their association with the host cells. Studies with blood trypomastigotes revealed that the swainsonine effect was reversible within 3 h. Two observations suggested that swainsonine had induced the parasite to produce defective oligosaccharides rich in mannose. First, swainsonine-treated organisms displayed a greater capacity to bind concanavalin than medium-treated organisms. Second, presence of alpha-methyl mannoside reduced such increased concanavalin A binding. Taken together, the present results suggest important roles for glycoprotein processing and oligosaccharide structures on the surface of both T. cruzi and its host cells in the initial stages of host cell infection.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001244:Association; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D006321:Heart / Q000469:parasitology*; D006790:Host-Parasite Interactions; D008264:Macrophages / Q000469:parasitology*; D008358:Mannose / Q000096:biosynthesis; D051379:Mice; D008808:Mice, Inbred CBA; D009844:Oligosaccharides / Q000096:biosynthesis; D017026:Swainsonine; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000378:metabolism*
D000470:Alkaloids; D006023:Glycoproteins; D009844:Oligosaccharides; D003208:Concanavalin A; D008358:Mannose; D017026:Swainsonine