Kinetic analysis of chemotactic peptide receptor modulation.

The dynamics of the chemotactic peptide receptor on rabbit peritoneal polymorphonuclear leucocytes were followed using the tritiated peptide N-formylnorleucylleucylphenylalanine (FNLLP). We have used a kinetic analysis to examine the possible interrelationships between receptor loss (down-regulation), receptor-mediated peptide uptake, and receptor recycling. We have previously demonstrated that cells incubated with FNLLP show a dose-dependent reduction in the number of receptors available on the surface. This receptor down-regulation is complete within 20 min and then the number of receptors available for binding remains at a plateau level. Peptide continues to be taken up in a receptor-mediated manner even after down-regulation is complete. If peptide is removed, receptor recovery occurs and does not require protein synthesis. In these studies we have investigated the kinetics of these processes. On the basis of this analysis, we propose that the plateau receptor level is a steady-state in which receptor internalization and return occur continuously. We demonstrate that the rate of receptor-mediated peptide uptake is approximately equal to the rate of receptor recovery measured after peptide removal. In addition, the rate of receptor recovery is proportional to the number of receptors missing from the surface, suggesting receptor recycling may be occurring.