(Received for publication, August 2, 1995, and in revised form, May 13, 1996)

From the Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109

Geneva M. Omann

From the Departments of Biological Chemistry and Surgery, University of Michigan Medical School and Veteran's Administration Medical Center, Ann Arbor, Michigan 48105

High resolution kinetic data of the binding of fluorescent peptide to the N-formyl peptide receptor of neutrophils at 37 °C has allowed for the development of a ligand binding model that predicts statistically larger binding rate constants than those previously reported for intact neutrophils. The new model accounts for ligand association and dissociation, receptor up-regulation, ligand-receptor complex internalization, a change in receptor affinity, and the quenching of internalized fluorescent ligand. We determined that receptor up-regulation is both agonist- and temperature-induced and is inhibited by both phenylarsine oxide and pertussis toxin treatment. Model fits of ligand association to pertussis toxin-treated cells show that while receptor up-regulation was inhibited, rate constants for ligand binding, receptor affinity conversion, and internalization of ligand-receptor complexes were unaffected. Results suggest G_i-protein-mediated receptor up-regulation and G_i-protein-independent receptor affinity conversion. Simulation of ligand infusion using our model gives insight into the quantitative and dynamic relationship between the low affinity ligand-receptor complex and the actin polymerization response.

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