DOSE-DEPENDENT PRIMING OR DESENSITIZATION INDUCED BY CHEMOTACTIC AGENTS IN CHEMILUMINESCENCE EXPERIMENTS WITH CANINE AND HUMAN NEUTROPHILS

We explored whether receptor-specific desensitization in repeated stim ulation offers an opportunity to identify chemotactic factors particul arly in species, e.g. the dog, for which immunochemical methods to det ermine chemotactic factors are not commercially available. Complement fragment 5a and interleukin-8 act via distinct receptors. They were us ed as test agents for neutrophils in luminol-dependent chemiluminescen ce. These experiments led to the observation that exposure of human an d canine neutrophils to low concentrations of a chemotactic agent show s an increased response when stimulated again with the Same agent (pri ming). In the heterologous system even cross-priming could be observed after a second stimulation with another agent. The concentration at w hich priming rather than desensitization occurred were lower for homol ogous factor-cell combinations (<10-20 nM) than for heterologous combi nations (<45-60 nM). The mechanism underlying this phenomenon is unkno wn. However, it raises the possibility that it subserves an important function in the recruitment and activation of cells by low agonist con centration. This study shows that despite the phenomenon of priming re ceptor-specific desensitization may be used to determine chemotactic a gents in the homologous system. (C) 1998 Elsevier Science B.V. All rig hts reserved.