The ablastin phenomenon: Inhibition of membrane function

Autoradiography of Trypanosoma lewisi labeled in vivo with 3H-thymidine (3HTdR) shows that the shortest doubling time for labeled organisms is 8 hr in intact and immunosuppressed rats. The parasite doubling time increases progressively after the fourth day of infection to 12 hr in immunosuppressed rats and to 24 hr or more in intact rats. The number of days following infection during which the trypanosomes reproduce is prolonged in immunosuppressed rats. In vitro studies of ablastin using 3HTdR-labeled trypanosomes confirmed that cell reproduction halts in the presence of ablastin, but resumes when the parasites are removed from the antibody. Several lines of evidence have been obtained, indicating that the primary effects of ablastin may be on membrane function. Thus, the saturable component for glucose transport in reproducing and ablastin inhibited trypanosomes has an average Km value of 2.8 × 10−4M, but the average Vmax values for glucose transport are reduced from 3.15 nmole/min/1.25 × 107 reproducing parasites to an average of 1.8 nmole/min/1.25 × 107 nonreproducing forms. Glucose transport is competitively inhibited by 2-deoxyd-glucose (2DOG). The exit and counterflow of 16C-2DOG from previously loaded trypanosomes is restricted in the presence of antiserum.