Dose-dependent priming or desensitization induced by chemotactic agents in chemiluminescence experiments with canine and human neutrophils

Abstract

We explored whether receptor-specific desensitization in repeated stimulation offers an opportunity to identify chemotactic factors particularly in species, e.g. the dog, for which immunochemical methods to determine chemotactic factors are not commercially available. Complement fragment 5a and interleukin-8 act via distinct receptors. They were used as test agents for neutrophils in luminol-dependent chemiluminescence. These experiments led to the observation that exposure of human and canine neutrophils to low concentrations of a chemotactic agent shows an increased response when stimulated again with the same agent (priming). In the heterologous system even cross-priming could be observed after a second stimulation with another agent. The concentration at which priming rather than desensitization occurred were lower for homologous factor-cell combinations (<10–20 nM) than for heterologous combinations (<45–60 nM). The mechanism underlying this phenomenon is unknown. However, it raises the possibility that it subserves an important function in the recruitment and activation of cells by low agonist concentration. This study shows that despite the phenomenon of priming receptor-specific desensitization may be used to determine chemotactic agents in the homologous system.