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Proteinase-activated receptor-2 up-regulation by Fcgamma-receptor activation in human neutrophils

Mireille St-Onge1, Stéphanie Lagarde, Cynthia Laflamme

  • 1Centre de Recherche en Rhumatologie et Immunologie du Centre Hospitalier Universitaire de Québec, Department of Microbiology-Infectiology and Immunology, Faculty of Medicine, Laval University, Quebec, Canada.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|February 16, 2010
PubMed

Insights

Human granulocytes up-regulate proteinase-activated receptor-2 (PAR-2) on their surface upon encountering bacteria. This enhances their response to proteinase activity, suggesting a stronger link between inflammation and pain signaling.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Proteinase-activated receptors (PARs) are implicated in inflammation and hyperalgesia.
  • The role of PARs in human granulocytes, particularly neutrophils, requires further elucidation.
  • Understanding PAR expression and function is crucial for inflammatory and pain pathway research.

Purpose of the Study:

  • To investigate the expression and function of the PAR family in human granulocytes.
  • To determine how bacterial stimulation affects PAR expression on granulocytes.
  • To explore the mechanisms underlying PAR-2 mobilization and its impact on cellular responsiveness.

Main Methods:

  • Analysis of PAR-1, PAR-2, PAR-3, and PAR-4 mRNA expression in resting human granulocytes.
  • Flow cytometry to assess cell surface expression of PAR-2 following stimulation with opsonized bacteria (Bop).
  • Measurement of intracellular calcium concentration changes to evaluate cellular response to PAR-2 activation.

Main Results:

  • Resting granulocytes constitutively expressed PAR-2 and PAR-3 mRNA.
  • Bacterial stimulation (Bop) led to a concentration- and time-dependent up-regulation of cell surface PAR-2, independent of new protein synthesis.
  • Preformed PAR-2 stored in primary granules was mobilized to the cell surface upon granule fusion.
  • Enhanced PAR-2 surface expression increased cellular responsiveness to PAR-2 activation, specifically dependent on immunoglobulin (Ig)-binding receptor engagement.
  • Neutrophils became more responsive to proteinase activity.

Conclusions:

  • Mobilization of intracellular granules, triggered by Ig-receptor activation, enhances PAR-2 surface expression in human granulocytes.
  • Increased PAR-2 surface expression augments neutrophil responsiveness to proteinase activity.
  • This heightened response suggests a more significant role for molecular communication between pain and inflammation pathways than previously understood.

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