MODULATION OF THE CHEMOTACTIC RESPONSIVENESS OF GUINEA-PIG NEUTROPHILS TO HRIL-8 AND FMLP

Neutrophils elicited in the peritoneal cavity of guinea pigs were puri fied on Percoll gradients and their chemotactic response to hrIL-8 and fMLP measured in vitro. hrIL-8 and fMLP were effective chemoattractan ts with optimal concentrations of 6 x 10(-9) and 1 x 10(-7) M, respect ively. Scatchard analysis revealed approximately 205,000 IL-8 receptor s/cell and 34,000 fMLP receptors/cell with KD values of 4.1 x 10(-9) a nd 3.3 x 10(-8) M, respectively. At suboptimal concentrations of chemo attractants the response was inhibited by dibutyryl cyclic AMP, histam ine, and adenosine in the presence of a phosphodiesterase inhibitor. I L-8 and fMLP induced an increase in cellular cyclic AMP and the respon se to optimal concentrations of chemoattractants was inhibited by Calp hostin C and Ro 31-8220, inhibitors of protein kinase C (PKC). Our res ults indicate that the chemoattractants activate the same PKC-dependen t pathway that is downregulated by cyclic AMP-dependent mechanisms.