TUMOR-NECROSIS-FACTOR-ALPHA ALTERS THE METABOLISM OF ENDOTHELIAL-CELLPROTEOGLYCANS

Cytokines play an important role in modulating cellular function. The effect of tumor necrosis factor alpha (TNF-alpha) on the metabolism of proteoglycans (PGs) was studied in mouse aortic endothelial cells (MA E). Confluent and exponentially growing cells were labeled with [S-35] sulfate and [H-3] glycine, and PGs isolated from the secreted, the pe ricellular, and intracellular pools. TNF-alpha influenced the metaboli sm of MAE PGs. This effect of TNF-alpha was dependent on the growth st ate of the cells. Nondividing MAE secrete PGs that have higher net neg ative charge than PGs from exponentially growing cells. TNF-alpha trea tment further increased the net negative charge of PGs secreted from n ondividing cells. Treatment of MAE with TNF-alpha caused a substantial decrease in the sulfation of PGs isolated from pericellular pool of n ondividing cells, while it had the opposite effect on pericellular PGs isolated from dividing cells. Our results indicate that changes in PG s metabolism induced by TNF-alpha may contribute to the disturbance of vascular endothelial homeostasis associated with vascular injury in a variety of disease states.