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Modulation of the chemotactic responsiveness of guinea pig neutrophils to hrIL‐8 and fMLP
Author(s) -
Dai Yalei,
Holgate Stephen T.,
Church Martin K.,
Shute Janis K.
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.56.6.776
Subject(s) - chemotaxis , calphostin c , protein kinase c , n formylmethionine leucyl phenylalanine , medicine , biology , endocrinology , receptor , percoll , chemotaxis assay , adenosine , in vitro , biochemistry , signal transduction
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 10 ‐9 and 1 10 ‐7 M, respectively. Scatchard analysis revealed approximately 205,000 IL‐8 receptors/cell and 34,000 fMLP receptors/cell with K d values of 4.1 10 ‐9 and 3.3 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. J. Leukoc. Biol. 56: 776–783; 1994.