Mechanisms of basal and cytokine-induced uptake of glucose in normal human eosinophils: relation to apoptosis.
A link between glucose transport and apoptosis was suggested. We studied the mechanisms of glucose transport in human eosinophils by means of the uptake of the positron emitting analogue, 18Fluoro-2-Deoxyglucose (FDG) and apoptosis by means of flow cytometry. FDG uptake was inhibited by antibodies to GLUT1, 3 and 4 and by cytochalasin B. The anti-apoptotic principles IL-5, GM-CSF, IL-3 enhanced the uptake, whereas the apoptosis-inducing principles anti-CD95 (anti-Fas) and exposure to serum-coated Sephadex particles caused a reduction. Also TNF-alpha enhanced the uptake. Other cytokines such as IL-2, IL-4, IL-8, RANTES and MCP-3 had no effect on the glucose uptake. 2-Deoxyglucose, antibodies to GLUT4 and CD95 induced apoptosis. The basal FDG-uptake was unaffected by PKC inhibitors Ro-31-8220, Gö-6983 and Gö-6976, whereas the latter inhibited the IL-5-enhanced uptake possibly due to the inhibition of PKC(mu). Protein tyrosine kinase and PI-3 kinase inhibitors inhibited IL-5-enhanced FDG-uptake only. In contrast MEK inhibitors inhibited the basal uptake only. Inhibitors of p38 MAPkinase inhibited both basal and IL-5 enhanced uptake. We conclude that glucose uptake in eosinophils is governed by specific intracellular mechanisms involving mobilization of GLUTs, Ca2+ and the activation of the MAP kinase pathway and that the IL-5-enhanced uptake uniquely seems to involve PKC(mu) activity. Our results suggest a close link between apoptosis and glucose transport in human eosinophils.
Venge
Per
P
Department of Medical Sciences, Clinical Chemistry, University of Uppsala, Uppsala, Sweden. per.venge@clm.uas.lul.se
Moberg
Lena
L
Björnsson
Eythor
E
Bergström
Mats
M
Långström
Bengt
B
Håkansson
Lena
L
D017209:Apoptosis / Q000502:physiology*; D001481:Basal Metabolism; D001692:Biological Transport; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004804:Eosinophils / Q000378:metabolism*; D005434:Flow Cytometry; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015398:Signal Transduction / Q000187:drug effects
D016207:Cytokines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose