Regulation of lipopolysaccharide-induced increases in neutrophil glucose uptake

Daniel P. Schuster, Steven L. Brody, Zhaohui Zhou, Matt Bernstein, Robert Arch, Daniel Link, Michael Mueckler

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

The pathogenesis of many lung diseases involves neutrophilic inflammation. Neutrophil functions, in turn, are critically dependent on glucose uptake and glycolysis to supply the necessary energy to meet these functions. In this study, we determined the effects of p38 mitogen-activated protein kinase and hypoxia-inducible factor (HIF)-1, as well as their potential interaction, on the expression of membrane glucose transporters and on glucose uptake in murine neutrophils. Neutrophils were harvested and purified from C57BL/6 mice and stimulated with lipolypolysaccharide (LPS) in the presence or absence of specific p38 and HIF-1 inhibitors. Glucose uptake was measured as the rate of [3H]deoxyglucose (DG) uptake. We identified GLUT-1 in mouse neutrophils, but neither GLUT-3 nor GLUT-4 were detected using Western blot analysis, even after LPS stimulation. LPS stimulation did not increase GLUT-1 protein levels but did cause translocation of GLUT-1 from the cell interior to the cell surface, together with a dose-dependent increase in [3H]DG uptake, indicating that glucose uptake is regulated in these cells. LPS also activated both p38 and the HIF-1 pathway. Inhibitors of p38 and HIF-1 blocked GLUT-1 translocation and [3H]DG uptake. These data suggest that LPS-induced increases in neutrophil glucose uptake are mediated by GLUT-1 translocation to the cell surface in response to sequential activation of neutrophil p38 and HIF-1α in neutrophils. Given that neutrophil function and glucose metabolism are closely linked, control of the latter may represent a new target to ameliorate the deleterious effects of neutrophils on the lungs.

Original languageEnglish (US)
Pages (from-to)L845-L851
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume292
Issue number4
DOIs
StatePublished - Apr 1 2007

Keywords

  • Deoxyglucose
  • GLUT-1
  • Hypoxia-inducible factor-1
  • p38

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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