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 iPLA 2 activity, arachidonic acid release, and PAF production. These tryptase-stimulated responses were inhibited by pretreatment with the iPLA 2-selective inhibitor bromoenol lactone (BEL; 5 μM, 10 min). Similar patterns of increased iPLA 2 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 iPLA 2, 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

Fingerprint

Tryptases
Endothelial cells
Calcium-Independent Phospholipase A2
Endothelium
Endothelial Cells
Platelet Activating Factor
P-Selectin
PAR-2 Receptor
Coronary Vessels
Neutrophils
Vascular System Injuries
Chemical activation
seryl-leucyl-isoleucyl--glycyl-lysyl-valine
Arachidonic Acid
Proteinase-Activated Receptors
Acoustic impedance
Electric Impedance
Monolayers
Adhesion
Epithelial Cells

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

@article{8054fefb09c94b28a69c5a9251f915c5,
title = "Potential role for mast cell tryptase in recruitment of inflammatory cells to endothelium",
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 iPLA 2 activity, arachidonic acid release, and PAF production. These tryptase-stimulated responses were inhibited by pretreatment with the iPLA 2-selective inhibitor bromoenol lactone (BEL; 5 μM, 10 min). Similar patterns of increased iPLA 2 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 iPLA 2, leading to arachidonic acid release, PAF production, cell surface P-selectin expression, and increased neutrophil adherence.",
author = "Meyer, {Maureen C.} and Michael Creer and Jane McHowat",
year = "2005",
month = "12",
day = "1",
doi = "10.1152/ajpcell.00215.2005",
language = "English (US)",
volume = "289",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "6 58-6",

}

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

TY - JOUR

T1 - Potential role for mast cell tryptase in recruitment of inflammatory cells to endothelium

AU - Meyer, Maureen C.

AU - Creer, Michael

AU - McHowat, Jane

PY - 2005/12/1

Y1 - 2005/12/1

N2 - 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 iPLA 2 activity, arachidonic acid release, and PAF production. These tryptase-stimulated responses were inhibited by pretreatment with the iPLA 2-selective inhibitor bromoenol lactone (BEL; 5 μM, 10 min). Similar patterns of increased iPLA 2 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 iPLA 2, leading to arachidonic acid release, PAF production, cell surface P-selectin expression, and increased neutrophil adherence.

AB - 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 iPLA 2 activity, arachidonic acid release, and PAF production. These tryptase-stimulated responses were inhibited by pretreatment with the iPLA 2-selective inhibitor bromoenol lactone (BEL; 5 μM, 10 min). Similar patterns of increased iPLA 2 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 iPLA 2, leading to arachidonic acid release, PAF production, cell surface P-selectin expression, and increased neutrophil adherence.

UR - http://www.scopus.com/inward/record.url?scp=27744443201&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27744443201&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00215.2005

DO - 10.1152/ajpcell.00215.2005

M3 - Article

VL - 289

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 6 58-6

ER -