Bioenergetics of human peripheral blood mononuclear cell metabolism in quiescent, activated, and glucocorticoid-treated states.
The first quantitative findings on the energy metabolism of human immune cells are presented. In quiescent peripheral blood mononuclear cells (PBMC) protein biosynthesis and Na+,K+-ATPase activity each accounted for 8% of cellular oxygen consumption. Stimulation with 25, 50, and 75 microg Con A/ml (1.25, 2.5 or 3.75 microg/10(6) cells) increased total oxygen consumption within seconds by 8, 36, and 53%, respectively. After addition of 75 microg Con A/ml, the proportion of cellular oxygen consumption due to protein biosynthesis, Na+,K+-ATPase activity, and Ca2+-ATPase activity was 15% each and that due to DNA/RNA synthesis was 8%. On the basis of these findings the immediate effects of five different glucocorticoids on cellular energy metabolism were investigated. The various glucocorticoids exerted basically the same inhibitory effects on Con A-stimulated cellular respiration and individual ATP-consuming processes, but differed significantly in potency. Similar to previous studies on rat thymocytes, the relative potencies of the glucocorticoids were found to be: prednylidene (1.7) > dexamethasone (1.5) > methylprednisolone (1.0) > prednisolone (0.3) > betamethasone (< 0.2). Given their rapidity of onset, these effects must be nongenomically mediated. The differences between the relative potencies of the various glucocorticoids for these effects and those for the classical genomic effects have important clinical implications, in particular for high-dose systemic and local glucocorticoid therapy.
Schmid
D
D
Department of Medicine (Rheumatology), Charité University Hospital, Humboldt University, Berlin, Germany.
Burmester
G R
GR
Tripmacher
R
R
Kuhnke
A
A
Buttgereit
F
F
D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D009696:Nucleic Acids / Q000096:biosynthesis; D010101:Oxygen Consumption / Q000187:drug effects; D014176:Protein Biosynthesis; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D005938:Glucocorticoids; D009696:Nucleic Acids; D003208:Concanavalin A; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase