HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/6/C1485    most recent 00215.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Meyer, M. C. Articles by McHowat, J. Search for Related Content PubMed PubMed Citation Articles by Meyer, M. C. Articles by McHowat, J.

VASCULAR BIOLOGY

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

Department of Pathology, Saint Louis University School of Medicine, St. Louis, Missouri

Submitted 4 May 2005 ; accepted in final form 28 July 2005

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.

atherosclerosis; endothelial cells

This article has been cited by other articles:

				I. Seitz, S. Hess, H. Schulz, R. Eckl, G. Busch, H. P. Montens, R. Brandl, S. Seidl, A. Schomig, and I. Ott Membrane-Type Serine Protease-1/Matriptase Induces Interleukin-6 and -8 in Endothelial Cells by Activation of Protease-Activated Receptor-2: Potential Implications in Atherosclerosis Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 769 - 775. [Abstract] [Full Text] [PDF]