title: Impairment of type III group B Streptococcus-stimulated superoxide production and opsonophagocytosis by neutrophils in diabetes.
abstract: The effect of hyperglycemia upon susceptibility to bacterial infection in diabetes mellitus is incompletely elucidated. The present experiments assessed the effect of hyperglycemia upon neutrophil-mediated phagocytosis of type III group B Streptococcus (GBS). Type III GBS was chosen for study because the incidence of invasive GBS disease is substantially increased in type 2 diabetic compared with nondiabetic subjects. The hypothesis tested was that severe hyperglycemia would alter neutrophil metabolism by diverting NADPH from superoxide production into the aldose reductase-dependent polyol pathway that converts glucose into sorbitol and thus would impair opsonophagocytosis (OP) of type III GBS. Neutrophils from 10 adults with type 2 diabetes had no intrinsic phagocytic defect under baseline glycemic conditions. After equilibration in 60 or 120 mM glucose or in 60 mM choline chloride, OP activity was reduced significantly (P < or = 0.03). Neutrophil superoxide production correlated with glucose concentration and also was significantly reduced during hyperglycemia (P < 0.05). Addition of III GBS capsular polysaccharide-specific IgG in a sufficient concentration supported efficient OP, even during hyperglycemia. Alrestatin, an aldose reductase inhibitor, increased superoxide production and significantly improved OP of type III GBS (P = 0.03). Thus, diversion of NADPH into the polyol pathway is one mechanism by which OP of GBS III is impaired during hyperglycemia, and this effect is mitigated when levels of capsular polysaccharide-specific IgG are sufficient.
authors.affiliation: Section of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Mazade
authors.forename: M S
authors.initials: MS
authors.lastname: Edwards
mesh_terms: D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D010587:Phagocytosis; D013292:Streptococcus agalactiae / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D007546:Isoquinolines; D013481:Superoxides; C016212:alrestatin; D000449:Aldehyde Reductase