Modulation of the chemotactic responsiveness of guinea pig neutrophils to hrIL-8 and fMLP

Y. Dai, S. Holgate, M. Church, Jan Shute

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Abstract

Neutrophils elicited in the peritoneal cavity of guinea pigs were purified on Percoll gradients and their chemotactic response to hrIL-8 and fMLP measured in vitro. hrIL-8 and fMLP were effective chemoattractants with optimal concentrations of 6 x 10(-9) and 1 x 10(-7) M, respectively. Scatchard analysis revealed approximately 205,000 IL-8 receptors/cell and 34,000 fMLP receptors/cell with KD values of 4.1 x 10(-9) and 3.3 x 10(-8) M, respectively. At suboptimal concentrations of chemoattractants the response was inhibited by dibutyryl cyclic AMP, histamine, and adenosine in the presence of a phosphodiesterase inhibitor. IL-8 and fMLP induced an increase in cellular cyclic AMP and the response to optimal concentrations of chemoattractants was inhibited by Calphostin C and Ro 31-8220, inhibitors of protein kinase C (PKC). Our results indicate that the chemoattractants activate the same PKC-dependent pathway that is down-regulated by cyclic AMP-dependent mechanisms.
Original languageEnglish
Pages (from-to)776-783
Number of pages8
JournalJournal of Leukocyte Biology
Volume56
Issue number6
Publication statusPublished - Dec 1994

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