The role of aldose reductase inhibition in diabetic neutrophil phagocytosis and killing.
This study examines whether an aldose reductase inhibitor (statil, ICI) can enhance neutrophil oxidative killing by diabetic neutrophils. We have examined a radiometric assay of phagocytosis and killing of Candida albicans by neutrophils from 20 controls and 20 subjects with insulin-dependent diabetes under various in vitro glucose concentrations. Glucose was present at 5, 10 and 20 mM in the presence and absence of statil (11 microM). Phagocytosis was unaffected by raised glucose levels in controls and in diabetic subjects. Killing by the diabetic cells was inhibited by increasing concentrations of glucose, killing was 18.9 +/- 2.0, 16.9 +/- 2.4 and 14.8 +/- 2.0% (mean +/- s.e.m.) at 5, 10 and 20 mM glucose, respectively (P less than 0.05). With the addition of statil under the same conditions killing improved to 19.3 +/- 2.0, 23.2 +/- 2.2 and 23.6 +/- 2.4 (P less than 0.01), these values were similar to the controls (P greater than 0.01). We conclude therefore that aldose reductase inhibition restores oxidative killing to normal.
Tebbs
S E
SE
Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, England.
Gonzalez
A M
AM
Wilson
R M
RM
D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D002176:Candida albicans / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009249:NADP / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010587:Phagocytosis; D010793:Phthalazines / Q000494:pharmacology*
D010793:Phthalazines; C042829:ponalrestat; D009249:NADP; D000449:Aldehyde Reductase; D005947:Glucose