The investigators have previously demonstrated that neonatal animals and humans possess a neutrophil system which is small, easily exhausted by infection, and unable to re-expand quickly. The present studies are designed to establish a model of neutrophil production, migration and kinetics in the developing rat, and to develop new strategies for managing neutropenic septic neonates. One group of experiments will examine the development of mature neutrophil and macrophage pools, as well as their precursors, during fetal life. In another set of experiments, the kinetics of neutrophils during experimental neonatal meningitis will be examined, as will their response to various therapeutic maneuvers. Finally, cytoplasts will be tested as potential substitutes for neutrophil transfusion, and attempts will be made to improve their function by intracellular loading with molecules conjugated to polylysine. It is anticipated that these studies will further clarify the factors which regulate the development of fetal granulocytopoiesis, and provide direction for new clinical strategies to manage the consequences of inadequate neonatal neutrophil supply.
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