Maternal administration of granulocyte colony-stimulating factor improves neonatal rat survival after a lethal group B streptococcal infection

Maternally administered recombinant human granulocyte colony- stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG- CSF augments neonatal defenses against a lethal bacterial challenge.     

Importance of catalase in the disposal of hydrogen peroxide within human erythrocytes

The catalase within normal, intact human erythrocytes was completely inactivated with amino triazole. The rate of 14CO2 evolution, when the cells were subsequently incubated with 14C-labeled glucose, provided a measure of the rate at which NADPH was being oxidized by the glutathione peroxidase/reductase system for the disposal of H2O2. This rate was determined in control cells and in catalase-inactivated cells while the cells were exposed to H2O2, which was generated at various constant and predetermined rates by glucose oxidase. The results indicated that catalase handles approximately half of the generated H2O2. The glutathione peroxidase/reductase mechanism accounted for the other half. These results are in agreement with our earlier findings on erythrocytes of a subject with a genetic deficiency of catalase. However, an unexpected result with the present approach was the finding that the increased dependence on the glutathione peroxidase/reductase mechanism did not occur until greater than 98% of the catalase had been inactivated. The latter observation indicates that catalase and the glutathione peroxidase/reductase system function intracellularly in a manner very different from that previously ascribed to them. An explanation of the findings requires that the two methods of H2O2 disposal function in a coordinated way, such as a sequential action in which the glutathione peroxidase/reductase system is the rate-limiting step.     

Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.