UNIDIRECTIONAL HETEROLOGOUS RECEPTOR DESENSITIZATION BETWEEN BOTH THEFMLP AND C5A RECEPTOR AND THE IL-8 RECEPTOR

During inflammation neutrophils receive multiple signals that art: int egrated, allowing a single modified response. One mechanism for this d iscrimination is receptor desensitization, a process whereby ligand-re ceptor binding is disassociated from cell activation. We examined the effect of heterologous receptor desensitization on neutrophil chemotax is, calcium mobilization, and arachidonic acid production, using inter leukin-8 (IL-8), C5a, and N-formyl-methionyl-leucyl-phenylalanine (fML P). We observed reciprocal inhibition with respect to chemotaxis, We d emonstrated that homologous desensitization, with respect to the mobil ization of intracellular calcium stores, lasted approximately 15 min. Heterologous desensitization between the fMLP receptor and the C5a rec eptor was reciprocal; either stimulant would diminish the cells' respo nse to stimulation by the other for approximately 3-5 min, However, we observed a unidirectional heterologous desensitization of the IL-8 re ceptor by both the fMLP and the C5a receptor, This unidirectional hete rologous desensitization was observed with respect to both calcium mob ilization and arachidonic acid production (i.e., prestimulation of the IL-8 receptor had no effect on subsequent stimulation by either fMLP or C5a).