Glucose suppresses superoxide generation in normal neutrophils: interference in phospholipase D activation
J. Ortmeyer and V. Mohsenin John B. Pierce Laboratory, Yale University School of Medicine, New Haven, Connecticut 06519. In neutrophils, N-formyl-Met-Leu-Phe (FMLP) stimulates a respiratory burst with subsequent generation of superoxide anion (O2-.) by NADPH oxidase. Signal transduction involved in...
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Veröffentlicht in: | American Journal of Physiology: Cell Physiology 1993-02, Vol.264 (2), p.C402-C410 |
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Zusammenfassung: | J. Ortmeyer and V. Mohsenin
John B. Pierce Laboratory, Yale University School of Medicine, New Haven, Connecticut 06519.
In neutrophils, N-formyl-Met-Leu-Phe (FMLP) stimulates a respiratory burst
with subsequent generation of superoxide anion (O2-.) by NADPH oxidase.
Signal transduction involved in this process includes FMLP receptor
stimulation of phosphoinositide hydrolysis with formation of inositol
1,4,5-trisphosphate and diacylglycerol and phosphatidylcholine hydrolysis
with formation of phosphatidic acid. Generation of these second messengers
would lead to activation of NADPH oxidase and generation of O2-..
Neutrophils from diabetic subjects and normal neutrophils exposed to
glucose have diminished ability to activate the respiratory burst in
response to various agonists. The mechanism of this suppression remains
unknown. We report herein that treatment of neutrophils with 15 and 50 mM
glucose significantly suppresses the O2-. formation in response to
receptor-mediated stimulation. The decreased O2-. generation is associated
with marked inhibition of phospholipase D (PLD) activity, with limited
hydrolysis of phosphatidylcholine and formation of phosphatidic acid.
Sorbitol (50 mM), a nonmetabolizable sugar with a similar osmotic effect,
has no influence on O2-. generation or PLD activation. The 4 beta-phorbol
12-myristate 13-acetate (PMA)-induced O2-. generation as well as PLD
activation are unaffected by glucose. Furthermore, the intracellular Ca2+
transient in response to FMLP is not influenced by glucose. Taken together,
these data suggest that glucose differentially interferes with activation
of PLD but not phospholipase C. And, the fact that PMA-induced activation
of PLD is not altered by glucose further suggests that a protein kinase C
independent step leading to the activation of PLD may be altered by
glucose. |
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ISSN: | 0363-6143 0002-9513 1522-1563 |
DOI: | 10.1152/ajpcell.1993.264.2.C402 |