Cellular Processing of Murine Colony-Stimulating Factor (Multi-CSF, GM-CSF, G-CSF) Receptors by Normal Hemopoietic Cells and Cell Lines

Abstract

The binding, internalization and degradation rates of three different murine colony-stimulating factors (Multi-CSF or interleukin-3, GM-CSF and G-CSF) and their receptor turnover rates were determined for normal bone marrow cells and a number of different cell lines at 37 degrees C. The kinetic parameters were extracted from a curve-fitting analysis of the approach to steady-state of surface-bound and internalized CSFs by methods described by Myers et al. (1987). The primary binding kinetic constants (association and dissociation) for each CSF on different cell types were similar, suggesting a single type of receptor for each CSF. In all cases, CSF binding induced a faster rate of internalization of occupied receptors than unoccupied receptors and resulted in significant accumulation of CSF inside the cell under steady-state conditions. The steady-state constant, determining the relationship between CSF concentration and receptor occupancy, indicated that, in all cases, more receptors were occupied at a given CSF concentration under steady-state conditions than would be under equilibrium conditions. Nevertheless, the data predicted that maximal biological effects of the CSFs were exerted at concentrations that did not result in full receptor occupancy. Comparison of the kinetic constants derived for the same CSF interacting with different types of cells or different CSFs interacting with the same cell type indicated that CSF and receptor processing resulted from a dynamic interplay of receptor-determined and cell-determined events. This resulted in a flexibility of the kinetic parameters that matched the variety of biological responses elicited by CSFs in different cell types.