Impaired surface expression of PAF receptors on human neutrophils is dependent upon cell activation

Weiguo Zhou, Martin A. Javors, Merle S. Olson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The capacity of human neutrophils to bind PAF was rapidly diminished upon cell stimulation with both physiological agonists (N-formylmethionylleucylphenylalanine (FMLP), leukotriene B4 (LTB4)) and pharmacologic agonists (phorbol 12-myristate 13-acetate (PMA), A23187). As a consequence, PAF responses in neutrophils were blunted, as monitored by an inhibition of intracellular Ca2+ mobilization. Downregulation of the PAF receptor in neutrophils by diverse agonists was temperature-sensitive and required intact cells. Scatchard analysis of binding data revealed that PAF binding sites were lost without an appreciable change in the affinity of the ligand for the receptor. The binding of the PAF receptor antagonist WEB2086 to neutrophils decreased in parallel with PAF binding. PMA-induced PAF receptor downregulation was stauro-sporine-sensitive while PAF receptor downregulation by A23187, FMLP, or LTB4 was staurosporine-resistant. Both neutrophil aggregation (a form of intercellular adhesion) and PAF receptor downregulation occurred only at high concentrations of agonists while other signaling processes such as the increase in [Ca2+]i, PKC activation, and PAF synthesis were stimulated at low concentrations of agonists. Furthermore, agonist-induced PAF receptor downregulation was observed only under conditions in which the activated neutrophils were stirred (or shaken) and were allowed to aggregate. Additionally, chelation of extracellular Ca2+ with EGTA minimized cell aggregation and also inhibited PAF receptor downregulation. While the nature of the biochemical signal or the physical changes in the plasma membrane associated with aggregation or that follow aggregation remain to be elucidated, it is clear that full expression of cell activation (i.e., neutrophil aggregation) is required for PAF receptor downregulation.

Original languageEnglish (US)
Pages (from-to)439-445
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume308
Issue number2
DOIs
StatePublished - Feb 1994

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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