Potential role for mast cell tryptase in recruitment of inflammatory cells to endothelium

Maureen C. Meyer, Michael Creer, Jane McHowat

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Recent research suggests that activation of protease-activated receptors (PARs) on the surface of endothelial and epithelial cells may play a role in general mechanisms of inflammation. We hypothesized that mast cell tryptase activation of endothelial cell PAR-2 is coupled to increased calcium-independent PLA2 (iPLA2) activity and increased platelet-activating factor (PAF) production that may play a role in inflammatory cell recruitment at sites of vascular injury. Stimulation of human coronary artery endothelial cells (HCAEC) with 20 ng/ml tryptase increased iPLA2 activity, arachidonic acid release, and PAF production. These tryptase-stimulated responses were inhibited by pretreatment with the iPLA2-selective inhibitor bromoenol lactone (BEL; 5 μM, 10 min). Similar patterns of increased iPLA2 activity and PAF production were also seen when HCAEC were treated with SLIGKV, which represents the tethered ligand sequence for the human PAR-2 once the receptor is cleaved by tryptase. Tryptase stimulation also increased cell surface expression of P-selectin, decreased electrical resistance, and increased neutrophil adherence to the endothelial cell monolayer. The tryptase-stimulated increases in both cell surface P-selectin expression and neutrophil adhesion were also inhibited with BEL pretreatment. We conclude that tryptase stimulation of HCAEC contributes importantly to early inflammatory events after vascular injury by activation of iPLA2, leading to arachidonic acid release, PAF production, cell surface P-selectin expression, and increased neutrophil adherence.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume289
Issue number6 58-6
DOIs
StatePublished - Dec 1 2005

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Tryptases
Endothelium
Endothelial Cells
Platelet Activating Factor
P-Selectin
PAR-2 Receptor
Coronary Vessels
Neutrophils
Vascular System Injuries
seryl-leucyl-isoleucyl--glycyl-lysyl-valine
Arachidonic Acid
Proteinase-Activated Receptors
Electric Impedance
Epithelial Cells
Ligands
Inflammation
Calcium
Research

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

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abstract = "Recent research suggests that activation of protease-activated receptors (PARs) on the surface of endothelial and epithelial cells may play a role in general mechanisms of inflammation. We hypothesized that mast cell tryptase activation of endothelial cell PAR-2 is coupled to increased calcium-independent PLA2 (iPLA2) activity and increased platelet-activating factor (PAF) production that may play a role in inflammatory cell recruitment at sites of vascular injury. Stimulation of human coronary artery endothelial cells (HCAEC) with 20 ng/ml tryptase increased iPLA2 activity, arachidonic acid release, and PAF production. These tryptase-stimulated responses were inhibited by pretreatment with the iPLA2-selective inhibitor bromoenol lactone (BEL; 5 μM, 10 min). Similar patterns of increased iPLA2 activity and PAF production were also seen when HCAEC were treated with SLIGKV, which represents the tethered ligand sequence for the human PAR-2 once the receptor is cleaved by tryptase. Tryptase stimulation also increased cell surface expression of P-selectin, decreased electrical resistance, and increased neutrophil adherence to the endothelial cell monolayer. The tryptase-stimulated increases in both cell surface P-selectin expression and neutrophil adhesion were also inhibited with BEL pretreatment. We conclude that tryptase stimulation of HCAEC contributes importantly to early inflammatory events after vascular injury by activation of iPLA2, leading to arachidonic acid release, PAF production, cell surface P-selectin expression, and increased neutrophil adherence.",
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Potential role for mast cell tryptase in recruitment of inflammatory cells to endothelium. / Meyer, Maureen C.; Creer, Michael; McHowat, Jane.

In: American Journal of Physiology - Cell Physiology, Vol. 289, No. 6 58-6, 01.12.2005.

Research output: Contribution to journalArticle

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