Albumin selectively inhibits TNF alpha-induced expression of vascular cell adhesion molecule-1 in human aortic endothelial cells

Leukocyte adhesion to, and transmigration across, the vascular endothelium are critical initiating steps in inflammation and atherosclerosis. We hypothesized that albumin, the major plasma protein, acts as an anti-inflammatory agent towards endothelial cells.

To test the hypothesis, we studied the effects of bovine serum albumin (BSA) on TNF alpha-induced expression of adhesion molecules in cultured human aortic endothelial cells (HAEC). We found that incubation of HAEC for 16 h with BSA (0.5-5%, w/v) dose-dependently inhibited TNF alpha-induced mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 nor E-selectin. Yeast recombinant human serum albumin exerted similar inhibitory effects on VCAM-1 expression, whereas gamma-globulin was ineffective. BSA also significantly inhibited TNF alpha-induced adhesion of monocytic THP-1 cells to HAEC in a dose-dependent manner. Furthermore, BSA strongly inhibited activation and nuclear translocation of the transcription factor, nuclear factor-kappa B (NF-kappa B). For example, the physiologically relevant concentration of 5% BSA inhibited NF-kappa B activation by 90+/-7%, VCAM-1 mRNA and protein expression by 81+/-4 and 80+/-13%, respectively, and THP-1 adhesion by 73+/-9% (n=3). The inhibitory effect of BSA on TNF alpha-induced VCAM-1 expression was not attenuated by inhibition of intracellular GSH synthesis.

Our data show that physiological concentrations of albumin selectively inhibit TNF alpha-induced upregulation of VCAM-1 expression and monocyte adhesion, most likely by inhibiting NF-kappa B activation in a GSH-independent manner.