Consequences of chemotactic peptide receptor modulation for leukocyte orientation

To exhibit chemotaxis, the orientation of locomotion along a chemical gradient cells sense differences in concentrations of a chemotactic factor by detecting some difference in the occupancy of their chemotactic receptors. Thus chemotaxis is sensitive to the number of receptors present and might be used to evaluate the consequences of receptor down-regulation. The ability of rabbit peritoneal polymorphonuclear leukocytes (PMNs) to orient to a standard gradient at various concentrations of N-formylnorleucylleucylphenylalanine (FNLLP) was examined. The observed orientation was compared to that expected if the directional signal were proportional to a difference in the absolute number or the fractional number of receptors occupied. The receptor occupancy in varying gradients was calculated from the binding constant of FNLLP, 2 X 10(-8) M (Zigmond and Sullivan, 1979, J. Cell Biol. 82:517-527), and the receptor number (a) present initially or (b) present after down-regulation (Sullivan and Zigmond, 1980, J. Cell Biol. 85:703-711). The observed concentration dependence of cell orientation is similar to the change in the number of receptors occupied, the receptor number being corrected for down-regulated cells. The net effect of receptor loss appears to be a decreased sensitivity to gradients at high concentrations of peptide.