Mechanism of ATP-induced leukocyte adherence to cultured pulmonary artery endothelial cells

Abstract

Previously we have shown that ATP enhances the adherence of HL-60 cells and human neutrophils to bovine pulmonary artery endothelial cells. The current investigations extend earlier findings by showing that ATP and UTP dose-dependently stimulate human neutrophil adherence to human pulmonary artery endothelial cells. We have also explore the mechanisms of ATP- and UTP-stimulated adherence. We have found that fucose, a component of selectin receptors, inhibits ATP-stimulated HL-60 cell-bovine pulmonary artery endothelial cell adhesion. Additionally, pretreatment of HL-60 cells with neuraminidase abolishes ATP enhancement. However, fucose does not affect ATP- or thrombin-induced adhesion of freshly isolated human neutrophils to human endothelial cells. Antibodies to human P-selection intercellular adhesion molecule (ICAM)-1, and the beta-subunit of CD11/CD18 do not alter ATP-induced adherence of HL-60 cells to bovine endothelial cells. Similarly, antibodies to human P-selectin and ICAM-1 do not inhibit human neutrophil-human pulmonary artery endothelial cell adhesion. The platelet-activating factor receptor antagonists, WEB-2086 and L-659,989, are effective in attenuating ATP- and UTP-stimulated adherence. Preincubation of neutrophils or human pulmonary artery endothelial cells with ATP or UTP also enhances adherence, an effect that is blocked by L-659,989. Thus platelet activating factor, associated with both neutrophils and endothelial cells, mediates ATP- and UTP-induced neutrophil adherence. ATP, released during vascular injury, may exacerbate neutrophil-endothelial cell interaction and thereby contribute to neutrophil-induced injury.

Reduced Atherosclerotic Lesions in P2Y 1 /Apolipoprotein E Double-Knockout Mice

“…Thus, these molecules have been reported to increase the expression of E-selectin on primary porcine or bovine aortic endothelial cells 35 ; to upregulate the secretion and expression of interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1 in dermal endothelial cells 36 ; and to increase the adhesion of leukocytes to endothelial cells. 37,38 It remains to be determined whether the endothelial P2Y 1 receptor could contribute to these phenomena. This would suggest that P2Y 1 displays a dual role, contributing to the antithrombogenic properties of endothelium by its role on nitric oxide and prostaglandin I 2 release under physiological conditions but also to endothelial cell activation under pathological conditions.…”

Purinergic signalling and cancer

“…Two different P2Y receptor subtypes were proposed to be responsible for the increase in [Ca 2+ ] i in HL60 cells, a P2Y 2 (or P2Y 4 ) receptor and probably a P2Y 1 receptor [447]. ATP enhanced the adherence of HL-60 cells to bovine pulmonary artery endothelial cells [448]. ATP increased cAMP production in undifferentiated HL-60 cells [449] and induced differentiation and suppressed cell growth via an unknown receptor (not P2Y 2 ) [450].…”

The P2Y2 Nucleotide Receptor Mediates UTP-induced Vascular Cell Adhesion Molecule-1 Expression in Coronary Artery Endothelial Cells

“…VCAM-1 expression is induced or up-regulated by proinflammatory cytokines such as TNF-␣ 1 and interleukin 1-␤ on cellular components of the arterial wall including endothelial cells, smooth muscle cells, and fibroblasts (13)(14)(15). ATP and UTP have been shown to induce cell-cell adhesion in a monocyte/macrophage lineage and neutrophil adherence to an endothelial cell monolayer (16,17), raising the possibility that released ATP and UTP could induce endothelial cell activation by an autocrine/paracrine mechanism to regulate leukocyte adherence.…”