Dynamics of human neutrophil receptors for the chemoattractant fmet-leu-phe

Neutrophils contain an intracellular pool of binding sites for the chemoattractant fmet-leu-phe with the same density as specific granules. This pool of receptors appears to be translocated to the plasma membrane during degranulation and may be important for receptor renewal during chemotaxis. Scatchard analyses of fmet-leu-phe binding to neutrophils and isolated plasma membranes are nonlinear and calculated Hill coefficients of binding to these fractions were about 0.67, suggesting negative cooperativity and/or heterogeneity of receptors. Some of the features of the nonlinear Scatchard curves may reflect heterogeneity of binding among cells since binding of fmet-leu-phe-lys-fluorescein to cells is heterogeneous when simultaneously monitored in the fluorescence activated cell sorter with a fluorescent probe of membrane potential. Following addition of a chemoattractant cells showing a depolarization have more chemoattractant associated with them than cells showing no change of membrane potential or a hyperpolarization. The cell associated chemoattractant is largely in a displaceable pool on the cells showing depolarization while it is in a nondisplaceable pool in the cells that either do not respond or show a hyperpolarization. Studies of the adaptation of human neutrophils responsiveness to fmet-leu-phe elicited membrane potential changes indicate that fmet-leu-phe stimulated decreases in receptor affinity accompany such adaptation. This decreased affinity appears to involve heterogeneity and/or negative cooperative interaction of receptors. The dynamics of chemoattractant receptors that have been reviewed provide further insights for studying the concepts behind the spatial and temporal mechanisms by which cells respond and adapt to a gradient of chemoattractant.