Neutrophil function and metabolism in individuals with diabetes mellitus

被引:214
作者
Alba-Loureiro, T. C.
Munhoz, C. D.
Martins, J. O.
Cerchiaro, G. A.
Scavone, C.
Curi, R.
Sannomiya, P.
机构
[1] InCor, Div Expt, BR-05403000 Sao Paulo, Brazil
[2] Univ Sao Paulo, Fac Med, BR-05508 Sao Paulo, Brazil
[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508 Sao Paulo, Brazil
[4] Univ Sao Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508 Sao Paulo, Brazil
[5] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo, Brazil
关键词
neutrophils; inflammation; diabetes mellitus; insulin; metabolism and cellular function;
D O I
10.1590/S0100-879X2006005000143
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Neutrophils act as first-line-of-defense cells and the reduction of their functional activity contributes to the high susceptibility to and severity of infections in diabetes mellitus. Clinical investigations in diabetic patients and experimental studies in diabetic rats and mice clearly demonstrated consistent defects of neutrophil chemotactic, phagocytic and microbicidal activities. Other alterations that have been reported to occur during inflammation in diabetes mellitus include: decreased microvascular responses to inflammatory mediators such as histamine and bradykinin, reduced protein leakage and edema formation, reduced mast cell degranulation, impairment of neutrophil adhesion to the endothelium and migration to the site of inflammation, production of reactive oxygen species and reduced release of cytokines and prostaglandin by neutrophils, increased leukocyte apoptosis, and reduction in lymph node retention capacity. Since neutrophil function requires energy, metabolic changes (i.e., glycolytic and glutaminolytic pathways) may be involved in the reduction of neutrophil function observed in diabetic states. Metabolic routes by which hyperglycemia is linked to neutrophil dysfunction include the advanced protein glycosylation reaction, the polyol pathway, oxygen-free radical formation, the nitric oxide-cyclic guanosine-3'-5' monophosphate pathway, and the glycolytic and glutaminolytic pathways. Lowering of blood glucose levels by insulin treatment of diabetic patients or experimental animals has been reported to have significant correlation with improvement of neutrophil functional activity. Therefore, changes might be primarily linked to a continuing insulin deficiency or to secondary hyperglycemia occurring in the diabetic individual. Accordingly, effective control with insulin treatment is likely to be relevant during infection in diabetic patients.
引用
收藏
页码:1037 / 1044
页数:8
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