Consequences of chemosensory phenomena for leukocyte chemotactic orientation

The stochastic nature of cell surface receptor-ligand binding is known to limit the accuracy of detection of chemoattractant gradients by leukocytes (11, 12), thus limiting the orientation ability that is crucial to the chemotactic response in host defense. The probabilistic cell orientation model of Lauffenburger (11) is extended here to assess the consequences of recently discovered receptor phenomena: "down-regulation" of total surface receptor number, spatial asymmetry of surface receptors, and existence of a higher-affinity receptor subpopulation. In general, a reduction in orientation accuracy is predicted by inclusion of these phenomena. An orientation signal based on a simple model of chemosensory adaptation (i.e., a spatial difference in relative receptor occupancy) is found to be functionally different from the signal suggested by an experimental correlation (i.e., a spatial difference in absolute receptor occupancy). However, in the context of receptor "signal noise," the signal based on adaptation yields predictions in better qualitative agreement with the experimental orientation data of Zigmond (10). From this cell orientation model we can estimate the effective timeaveraging period required for noise diminution to a level allowing orientation predictions to match observed levels. This time-averaging period presumably reflects the time constant for receptor signal transduction and locomotory response.