Effect of pentosan polysulfate sodium on adhesion molecule expression in canine endothelial cells and neutrophils

抄録

Pentosan polysulfate sodium (PPS) is a semi-synthetic sulfated polysaccharide with a heparin-like structure, known for its anticoagulant and anti-inflammatory properties. This study investigated the effect of PPS on adhesion molecules involved in neutrophil–endothelial interactions using an in vitro canine model. Canine aortic endothelial cells (CnAOEC) and neutrophils were pretreated with various concentrations of PPS and stimulated with recombinant canine tumor necrosis factor-alpha (rh-cTNFα). The mRNA expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), P-selectin, C-X-C motif chemokine receptor 2 (CXCR2), P-selectin glycoprotein ligand-1 (PSGL-1), and L-selectin was measured through real-time polymerase chain reaction (qPCR). C-X-C motif chemokine ligand 1 (CXCL1) secretion was quantified by enzyme-linked immunosorbent assay (ELISA). Lymphocyte function-associated antigen-1 (LFA-1/CD11a) expression was examined using flow cytometry. A static adhesion assay was used to evaluate the effect of PPS on neutrophil adhesion to endothelial cells. In conclusion, PPS displayed no cytotoxicity toward CnAOEC, and endothelial P-selectin expression was significantly reduced. Other adhesion molecules showed no significant differences compared with controls. CXCL1 secretion and neutrophil gene expression (CXCR2, PSGL-1, and L-selectin) varied slightly, although without statistical significance. PPS did not affect CD11a expression or neutrophil adhesion to endothelial cells. These results indicate that PPS is non-cytotoxic and may weakly modulate selectin-mediated endothelial activation without affecting integrin- or chemokine-dependent adhesion.