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, calciumindependent phospholipase A 2 (iPLA 2 ) 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.

Phospholipase A2 activity is associated with structural brain changes in schizophrenia

“…The classification of our target enzyme activity as intracellular is based on previous methodical investigations (Lasch et al, 2003) showing an almost complete (more than 90%) inhibitory effect of calcium ions on enzyme activity and a 70% inhibition of the enzyme activity by bromoenole lactone (BEL), a complete inhibitor of iPLA 2 (Jenkins et al, 2001;Lucas et al, 2005;Song et al, 2006;White and McHowat, 2007). As cPLA 2 has ubiquitary action with only micromolar calcium concentrations, it might also have contributed to the measured PLA 2 activity here.…”

Phospholipase A2activity in first episode schizophrenia: Associations with symptom severity and outcome at week 12

“…Most of the intracellular PLA 2 enzymes need calcium in micromolar concentrations at most (cPLA 2 ) or are completely independent of calcium (iPLA 2 ). The activity of enzymes obtained from the subjects in this study were almost completely (more than 90%) inhibited by calcium ions and strongly (70%) inhibited by bromoenole lactone (BEL), a total inhibitor of iPLA 2 (Jenkins et al 2001;Lucas et al 2005;Song et al 2006;White and McHowat 2007). In contrast, previous studies excluded the contribution of PAFhydrolases to the measured activity level, as PAF-hydrolases do not cleave the here used NBDC 6 -HPC ® substrate.…”

Polymorphonuclear leukocytes isolated from umbilical cord blood as a useful research tool to study adherence to cell monolayers

“…Leukocytes express a PAF receptor that enhances their endothelial cell adhesion and induces their β-integrin-mediated transmigration (Prescott et al, 2002). In previous studies, we have shown that thombin- or tryptase-stimulated endothelial cells demonstrate increased calcium-independent phospholipase A 2 activity, resulting in increased PAF production and PMN adherence (Kell et al, 2003; Vinson et al, 2005; McHowat et al, 2001; Rickard et al, 2005; Meyer et al, 2005; White and McHowat, 2007a; White et al, 2007b). We have shown that methyl arachidonyl fluorophosphonate (MAFP) inhibits PAF acetylhydrolase (PAF-AH) the enzyme responsible for PAF degradation, and increases PAF production and PMN adherence to endothelial cell monolayers (Kell et al, 2003; Vinson et al, 2005).…”