Neutrophil phagocytosis and killing in insulin-dependent diabetes.
Neutrophil phagocytosis and killing of Candida albicans were examined using a radiometric assay in 25 patients with insulin-dependent diabetes and 17 controls under various in vitro metabolic conditions. Glucose was present at 5, 10 and 50 mM, beta-hydroxybutyrate at 1, 5 and 20 mM and glucose with beta-hydroxybutyrate in combinations of 10 with 5 and 50 with 20 mM, respectively. Phagocytosis occurred at similar levels in diabetics and controls at all the glucose and beta-hydroxybutyrate concentrations used. The ability to neutrophils from diabetics to kill candida was inhibited by increased concentrations of glucose and beta-hydroxybutyrate, both independently and in combination. Candida killing (mean +/- s.e.) was 20 +/- 2.4, 19 +/- 2.3 and 13 +/- 2.7% at glucose concentrations of 5, 10 and 50 mM; and 20 +/- 3.4, 20 +/- 3 and 13 +/- 3% at beta-hydroxybutyrate concentrations of 1, 5 and 20 mM, respectively, and in glucose and beta-hydroxybutyrate combinations of 10 with 5 and 50 with 20 mM was 20 +/- 2.8 and 10 +/- 2.8%, respectively. Inhibition was not observed with control neutrophils. These data indicate that although phagocytosis occurs at similar levels in diabetics and controls, killing of candida by the diabetic neutrophil is impaired under conditions of hyperglycaemia and ketosis. The biochemical basis for this effect is discussed.
Wilson
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Reeves
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D020155:3-Hydroxybutyric Acid; D000293:Adolescent; D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000378:metabolism; D002176:Candida albicans; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000201:enzymology; D016883:Diabetic Ketoacidosis / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects
D006885:Hydroxybutyrates; D000449:Aldehyde Reductase; D005947:Glucose; D020155:3-Hydroxybutyric Acid