Apolipoprotein E acts to increase nitric oxide production in macrophages by stimulating arginine transport.

Journal Article

Previous studies have shown that apolipoprotein E (apoE) plays a role in immune function by modulating tissue redox balance. Using a mouse macrophage cell line (RAW 264.7), we have examined the mechanism by which apoE regulates nitric oxide (NO) production in macrophages. ApoE potentiates NO production in immune activated RAW cells in combination with lipopolysaccharide or polyinosinic:polycytidylic acid (PIC), agents known to induce expression of inducible nitric oxide synthase mRNA and protein. The effect is not observed with apolipoprotein B or heat-inactivated apoE. The combination of PIC plus apoE produced more NO than the level expected from an additive effect of PIC and apoE alone. Furthermore, this increase was observed at submaximal extracellular arginine concentrations, suggesting that apoE altered arginine (substrate) availability. Examination of [(3)H]arginine uptake across the cell membrane demonstrated that arginine uptake was increased by PIC but further increased by PIC plus apoE. Treatment of RAW cells with apoE was associated with an increased apparent V(max) and decreased affinity for arginine as well as a switch in the induction of mRNA for subtypes of cationic amino acid transporters (CAT). Treatment of RAW cells with PIC plus apoE resulted in the loss of detectable CAT1 mRNA and expression of CAT2 mRNA. Regulation of arginine availability is a novel action of apoE on the regulation of macrophage function and the immune response.

Full Text

Duke Authors

Cited Authors

  • Colton, CA; Czapiga, M; Snell-Callanan, J; Chernyshev, ON; Vitek, MP

Published Date

  • February 14, 2001

Published In

Volume / Issue

  • 1535 / 2

Start / End Page

  • 134 - 144

PubMed ID

  • 11342002

International Standard Serial Number (ISSN)

  • 0006-3002

Language

  • eng

Conference Location

  • Netherlands