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Stimulation and priming of human neutrophils by interleukin-8: cooperation
with tumor necrosis factor and colony-stimulating factors
A Yuo, S Kitagawa, T Kasahara, K Matsushima, M Saito and F Takaku
Clinical Research Institute, National Medical Center, Tokyo, Japan.
Interleukin-8 (IL-8) stimulated an increase in cytoplasmic-free Ca2+
([Ca2+]i) and intracellular pH (pHi) in parallel at low concentrations (0.5
to 5 ng/mL), and stimulated O2- release and membrane depolarization in
parallel at high concentrations (50 to 5,000 ng/mL). IL-8-induced O2-
release was potentiated by tumor necrosis factor (TNF),
granulocyte-macrophage colony-stimulating factor (GM-CSF), and
granulocyte-CSF (G-CSF) in a dose-dependent manner, whereas it was
inhibited by cyclic AMP agonists. These characteristics and the time-
courses of the responses stimulated by IL-8 were similar to those
stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP), except that
the cells stimulated by IL-8 showed shorter duration and less magnitude in
some responses. In addition, IL-8 was found to be a potent priming agent
and to enhance O2- release stimulated by FMLP. The priming effect of IL-8
was very rapid and was maximal within 5 minutes of preincubation. The
dose-response curves for priming were identical to those for triggering of
an increase in [Ca2+]i and pHi. The potency of the maximal priming effects
on FMLP-induced O2- release was TNF greater than GM-CSF greater than IL-8
greater than G-CSF. The combination of IL-8 and the suboptimal
concentrations of TNF or GM-CSF resulted in the additive priming effect,
whereas the combination of the optimal concentration of IL-8 and the
optimal concentration of TNF, GM- CSF, or G-CSF resulted in the effect of
more potent priming agent alone. These findings suggest that IL-8
stimulates or primes human neutrophils according to its concentrations and
cross-talks with TNF, GM-CSF, G-CSF, or FMLP at the inflammatory sites.
Volume 78,
Issue 10,
pp. 2708-2714,
11/15/1991
Copyright © 1991 by The American Society of Hematology
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