Platelet-activating factor may participate in signal transduction processes in rabbit leukocytes

A G Stewart1, T Harris

  • 1Department of Physiology, University of Melbourne, Victoria, Australia.

Lipids
|December 1, 1991
PubMed

Insights

Formyl-methionyl-leucyl-phenylalanine (fMLP) triggers platelet-activating factor (PAF) generation in rabbit leukocytes. Endogenous PAF appears to play a role in fMLP-induced signaling pathways.

Area of Science:

  • Immunology
  • Cellular Biology
  • Biochemistry

Background:

  • The bacterial peptide formyl-methionyl-leucyl-phenylalanine (fMLP) is a potent activator of polymorphonuclear leukocytes (PMNs).
  • fMLP is known to induce various cellular responses, including the generation of platelet-activating factor (PAF) and superoxide anion (O2-).

Purpose of the Study:

  • To investigate the role of endogenous platelet-activating factor (PAF) in the signaling cascade initiated by formyl-methionyl-leucyl-phenylalanine (fMLP) in rabbit polymorphonuclear leukocytes (PMNs).

Main Methods:

  • Rabbit PMNs were stimulated with fMLP and A23187.
  • The effects of PAF receptor antagonists (WEB 2086, CV 6209), a phospholipase A2 inhibitor (chloroquine), and a serine protease inhibitor (tosyl-phenylalanine chloromethyl ketone) on arachidonic acid mobilization, O2- generation, and PAF production were assessed.
  • The respiratory burst induced by phorbol myristate acetate was used as a control.

Main Results:

  • PAF receptor antagonists inhibited fMLP-induced arachidonic acid mobilization and O2- generation, but not A23187-induced responses.
  • Inhibitors of PAF synthesis (chloroquine, tosyl-phenylalanine chloromethyl ketone) reduced fMLP-stimulated PAF and O2- generation.
  • These inhibitors did not affect the respiratory burst induced by phorbol myristate acetate.

Conclusions:

  • Endogenous PAF production is involved in the fMLP-induced signaling pathway in rabbit PMNs.
  • These findings suggest that PAF acts as an intermediary in the fMLP signal transduction cascade.

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