Cytokine modulation of glutamine transport by pulmonary artery endothelial cells

The effects of tumor necrosis factor and interleukin-1 on sodium-dependent glutamine transport by cultured pulmonary artery endothelial cells (PAECs) were studied. Incubation of PAECs with cytokines (10 to 1000 units/ml) resulted in a significant increase in System ASC-mediated glutamine transport that was dose-dependent, first observable after 8 hours, and maximal after 12 hours of exposure. Kinetic studies indicated that the increase in carrier-mediated activity was not due to a change in Km (transporter affinity) but instead to a 45% to 75% increase in maximal transport rate (Vmax). The cytokine-stimulated increase in glutamine uptake by PAECs was completely blocked by actinomycin D and cycloheximide, indicating that the accelerated glutamine transport was dependent on de novo RNA and protein synthesis, perhaps of the transporter itself. The data indicate that these cytokines accelerate glutamine uptake by PAECs, either directly or indirectly, a response which may be required to support endothelial metabolism, structure, and function during infection and inflammation. The results of this study represent, to our knowledge, the first reports of cytokine-mediated modulation of System ASC activity, a carrier that has historically been unresponsive to hormonal regulation in other tissues.