Modeling complex neutrophil dynamics in the grey collie

We have developed a mathematical model for the peripheral regulation of neu trophil production mediated by granulocyte colony-stimulating factor. We ha ve used that model to show that the pattern of neutrophil oscillations in n ine grey collies is consistent with the hypothesis that cyclical neutropeni a is due to an oscillatory stem cell input to the neutrophil regulatory sys tem, and not due to autonomous oscillations in the peripheral neutrophil re gulatory system. In the process of interfacing our model with the laborator y data, we have estimated parameters for the peripheral neutrophil control system consistent with higher than normal apoptotic cell loss within the re cognizable neutrophil precursors. This is in agreement with other experimen tal data. Our estimated model parameters also predict that the peripheral n eutrophil production system is globally stable in the grey collies we studi ed. This further supports our hypothesis that the origin of the oscillatory behavior in cyclical neutropenia is in the stem cell population, consisten t with other clinical and experimental evidence. (C) 2000 Academic Press.