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, Volume 41, Supplement 2, pp C185–C187 | Cite as

Role of PAF in zymosan-induced IL-8 release from human neutrophils

  • Bo-ting Au
  • P. D. Collins
  • T. J. Williams
Proceedings of the Joint World Congress of the International Association of Inflammation Societies and the European Inflammation Society, Austria Center, Vienna, October 10–15, 1993 Inhibitors of Cytokine Generation and Action

Abstract

Stimulation of human neutrophils with zymosan particles resulted in a dose-response release of IL-8 in the 24 h culture supernatant, measured using a specific radioimmunoassay. IL-8 was detected after 8 h (0.11±0.08 nM) and peaked at 24 h (2.81±0.85 nM). Two distinct PAF receptor antagonists, WEB 2086 and UK 74505 produced a dose-dependent inhibition of zymosan-induced IL-8 release. This inhibitory action was maximal (68% 10−6M WEB 2086; 71% 10−8M UK 74505) when the drug was co-administered with zymosan, becoming progressively less effective when administered at increasing intervals after addition of zymosan. In contrast, a specific LTB4 antagonist, LY 255283, an IL-1 receptor antagonist and an anti-human TNFα antibody were unable to modulate the response indicating that these mediators are not involved. This study provides the first direct evidence of a central role for the phospholipid mediator PAF in the pathway of IL-8 release, following neutrophil activation by a particulate stimulusin vitro.

Keywords

Receptor Antagonist Inhibitory Action Culture Supernatant Direct Evidence Human Neutrophil 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Birkhäuser Verlag 1994

Authors and Affiliations

  • Bo-ting Au
    • 1
  • P. D. Collins
    • 1
  • T. J. Williams
    • 1
  1. 1.Department of Applied PharmacologyNational Heart and Lung InstituteLondonUK

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