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Protease activation of calcium-independent phospholipase A2 leads to neutrophil recruitment to coronary artery endothelial cells.

Abstract：

INTRODUCTION:Thrombin or tryptase cleavage of protease-activated receptors (PAR) on human coronary artery endothelial cells (HCAEC) results in activation of a membrane-associated, calcium-independent phospholipase A2 (iPLA2) that selectively hydrolyzes plasmalogen phospholipids. Atherosclerotic plaque rupture results in a coronary ischemic event in which HCAEC in the ischemic area would be exposed to increased thrombin concentrations in addition to tryptase released by activated mast cells present in the plaque. MATERIALS AND METHODS:HCAEC were stimulated with thrombin or tryptase in the absence or presence of bromoenol lactone (BEL), a selective iPLA2 inhibitor, and iPLA2 activation, accumulation of biologically active membrane phospholipid-derived metabolites, upregulation of cell surface P-selectin expression and neutrophil adherence were measured. RESULTS:HCAEC exposed to thrombin or tryptase stimulation demonstrated an increase in iPLA2 activity and arachidonic acid release. Additionally, stimulated HCAEC demonstrated increased platelet-activating factor (PAF) production and cell surface P-selectin expression, resulting in increased adhesion of neutrophils to HCAEC monolayers. Pretreatment with bromoenol lactone to inhibit iPLA2, blocked membrane phospholipid-derived metabolite production, increased cell surface P-selectin expression and neutrophil adherence. CONCLUSIONS:The similar biochemical and cellular responses in HCAEC exposed to thrombin or tryptase stimulation suggest that the cleavage of two separate PAR serve to extend the range of proteases to which the cells respond rather than resulting in separate intracellular events. This suggests that in conditions such as thrombosis and atherosclerosis that multiple mechanisms can activate the inflammatory response.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

White MC,McHowat J

doi

10.1016/j.thromres.2006.11.007

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

597-605

issue

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(06)00475-0

journal_volume

120

pub_type

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Protease activation of calcium-independent phospholipase A2 leads to neutrophil recruitment to coronary artery endothelial cells.