Trypanosoma cruzi: parasite-induced release of lysosomal enzymes by human polymorphonuclear leukocytes.
The release of beta-glucuronidase and lysozyme from human polymorphonuclear leukocytes (PMN) engaged in phagocytosis and lysis of Trypanosoma cruzi epimastigotes was studied in the presence or absence of chagasic serum. Lysosomal enzyme release was enhanced when parasites were sensitized with serum from a chronic Chagas' patient, increased up to 3 hr of incubation at 28 C, and depended on the PMN:parasite ratio. The release of lysosomal enzymes was determined by the presence of 2 mM cyanide, 2 microM azide, 3 mM amobarbital, and 1 mM phenylbutazone. These drugs inhibited the killing of sensitized T. cruzi by interfering with the oxidative microbicidal mechanisms of PMN without affecting the uptake of the parasites. Lysosomal enzyme release occurred in the presence of cyanide and azide, indicating that in these cases the enzymatic release was unrelated to the killing of the parasites. Amobarbital and phenylbutazone, which stabilize PMN membranes, inhibited the release of beta-glucuronidase and lysozyme by PMN. The addition of 10 micrograms/ml of cytochalasin B inhibited the phagocytosis and killing of sensitized T. cruzi by PMN but increased the enzymatic release by effector cells. Since cytochalasin B did not affect the close contact between PMN and parasites, it appears that the enzymes released to the extracellular milieu were not toxic to noningested parasites. Furthermore, the lysosomal enzymes did not lyse bystander unsensitized parasites. Therefore, the release of lysosomal enzymes during the interaction of T. cruzi epimastigotes and PMN seems to be related to the triggering event of the phagocytic process and does not bear a cause-effect relationship with parasite death.
D000654:Amobarbital / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D014355:Chagas Disease / Q000097:blood; D003486:Cyanides / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D009113:Muramidase / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology; D010587:Phagocytosis; D010653:Phenylbutazone / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000502:physiology*
D001386:Azides; D003486:Cyanides; D003571:Cytochalasin B; D009113:Muramidase; D005966:Glucuronidase; D010653:Phenylbutazone; D000654:Amobarbital