Lysoplasmenylcholine increases neutrophil adherence to human coronary artery endothelial cells

Abstract

We demonstrated previously that thrombin stimulation of human coronary artery endothelial cells (HCAEC) results in release of choline lysophospholipids [lysophosphatidylcholine (lysoPtdCho) and lysoplasmenylcholine (lysoPlsCho)]. These amphiphilic metabolites have been implicated in arrhythmogenesis following the onset of myocardial ischemia, but studies examining their direct effects on the vasculature remain limited. We and others have shown that thrombin and lysoPtdCho can increase cell surface adhesion molecules and adherence of circulating inflammatory cells to the endothelium. This study supports our hypothesis that these changes may be mediated, at least in part, by lysoPlsCho, thus implicating this metabolite as an inflammatory mediator in the coronary vasculature and a modulator of the progression of atherosclerosis. Apical stimulation of HCAEC with thrombin resulted in the production and release of choline lysophospholipids from the apical surface of the HCAEC monolayer. Basolateral stimulation had no effect on choline lysophospholipid production or release from either the apical or basolateral surface of the HCAEC monolayer. Incubation of HCAEC with lysoPlsCho or lysoPtdCho resulted in similar increases in HCAEC surface expression of P-selectin and E-selectin. Furthermore, lysoPlsCho increased cell surface expression of P-selectin, E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 with a time course similar to that of thrombin stimulation. Increased presence of cell surface adhesion molecules may contribute to the significant increase in adherence of neutrophils to either thrombin- or lysoPlsCho-stimulated HCAEC. These results demonstrate that the presence of thrombin at sites of vascular injury in the coronary circulation, resulting in increased choline lysophospholipid release from the HCAEC apical surface, has the potential to propagate vascular inflammation by upregulation of adhesion molecules and recruitment of circulating inflammatory cells to the endothelium.

Effect of quercetin and its metabolite on caveolin-1 expression induced by oxidized LDL and lysophosphatidylcholine in endothelial cells

“…( 32 ) In endothelial cells, lysoPC is known to participate in expression of adhesion molecules ICAM-1, ( 33 ) VCAM-1, ( 33 ) and P-selectin. ( 34 ) LysoPC appears to be a plausible endothelial cell activator, as lysoPC could induce CAV-1 expression at a lower concentration (0.1 µM) compared with 13-HPODE (10 µM). Thus, we deduced that lysoPC is at least partly responsible for the inductive effect of ox-LDL on CAV-1 expression.…”

From peroxisomal disorders to common neurodegenerative diseases – the role of ether phospholipids in the nervous system

“…B), which can also serve as second messengers. Lysoplasmalogens with an ethanolamine head group have the potential to act as self antigens in the stimulation and maturation of semi‐invariant natural killer cells ; those with a choline head group are able to induce increased adherence of neutrophils to human endothelial cells , possibly by activating a cAMP‐dependent protein kinase . The current knowledge on the functions of lysoplasmalogen in the nervous system is limited, but presumably some roles in signaling apply as well here.…”

Purification, Identification, and Cloning of Lysoplasmalogenase, the Enzyme That Catalyzes Hydrolysis of the Vinyl Ether Bond of Lysoplasmalogen

“…Lysoplasmalogens are amphiphilic molecules, and at levels near their critical micelle concentration, they produce membrane-perturbing effects and cell lysis (10). Lysoplasmalogens increase membrane fluidity and are involved in cell fusion (11) and cause circulating inflammatory cells to migrate to the endothelium (12). Lysoplasmenylcholine activates cAMP-dependent protein kinase A, suggesting involvement in signal transduction (13).…”