Increased polymorphonuclear leukocyte respiratory burst function in type 2 diabetes

Hand, W. Lee; Hand, D L; Vasquez, Yvonne

doi:10.1016/j.diabres.2006.07.015

Cited by 49 publications

(33 citation statements)

References 44 publications

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“…Several groups have reported that patients with diabetes or hyperglycemia exhibit aberrant neutrophil responses (1,3,12,14,33,34). Other investigators, however, failed to detect a defect in neutrophil function (18,28). These discrepancies could be attributed to the metabolic status of the diabetic patients, differences in methodology, or underlying diseases or complications among the population groups.…”

Section: Discussionmentioning

confidence: 69%

“…Whereas only ϳ20% of resting neutrophils from control mice were activated in the presence of medium alone, ϳ40% of resting neutrophils from the blood of db/db mice were activated. Several studies have demonstrated that resting neutrophils from diabetic patients exhibit an augmented oxidative burst activity compared with resting neutrophils from nondiabetic controls (2,18,24). Chronic exposure to low levels of reactive oxygen species may contribute to vascular complications and the development of chronic low-grade inflammation commonly found in diabetic hosts (41).…”

Section: Discussionmentioning

confidence: 99%

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Defects in Innate Immunity Predispose C57BL/6J-Lepr^db/Lepr^dbMice to Infection byStaphylococcus aureus

et al. 2009

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Foot and ankle infections are the most common cause of hospitalization among diabetic patients, and Staphylococcus aureus is a major pathogen implicated in these infections. Patients with insulin-resistant (type 2) diabetes are more susceptible to bacterial infections than nondiabetic subjects, but the pathogenesis of these infections is poorly understood. C57BL/6J-Lepr db /Lepr db (hereafter, db/db) mice develop type 2 diabetes due to a recessive, autosomal mutation in the leptin receptor. We established a S. aureus hind paw infection in diabetic db/db and nondiabetic Lepr +/+ (+/+) mice to investigate host factors that predispose diabetic mice to infection. Nondiabetic +/+ mice resolved the S. aureus hind paw infection within 10 days, whereas db/db mice with persistent hyperglycemia developed a chronic infection associated with a high bacterial burden. Diabetic db/db mice showed a more robust neutrophil infiltration to the infection site and higher levels of chemokines in the infected tissue than +/+ mice. Blood from +/+ mice killed S. aureus in vitro, whereas db/db blood was defective in bacterial killing. Compared with peripheral blood neutrophils from +/+ mice, db/db neutrophils demonstrated a diminished respiratory burst when stimulated with S. aureus. However, bone marrow-derived neutrophils from +/+ and db/db mice showed comparable phagocytosis and bactericidal activity. Our results indicate that diabetic db/db mice are more susceptible to staphylococcal infection than their nondiabetic littermates and that persistent hyperglycemia modulates innate immunity in the diabetic host.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Defects in Innate Immunity Predispose C57BL/6J-Lepr^db/Lepr^dbMice to Infection byStaphylococcus aureus

et al. 2009

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“…The metabolic cues or the damage that occurs within the mitochondria can culminate in wide-ranging changes in nuclear gene expression via a retrograde signaling from mitochondria to nucleus [25,26]. Recent investigations have pointed to a role of mitochondrial oxidative stress in modulating neutrophil functional ability in T2DM [27,28]. On similar lines, in our study the free radical overproduction observed in the form of H 2 O 2 generation along with diminished antioxidant enzymes SOD and GR activities in neutrophils of both early and late diabetic groups was attributed to an adaptive reaction of oxidative stress in mitochondria (Figs.…”

Section: Discussionmentioning

confidence: 99%

Impairment of Mitochondrial–Nuclear Cross Talk in Neutrophils of Patients with Type 2 Diabetes Mellitus

Khan

Raghuram²,

Pathak

et al. 2013

Ind J Clin Biochem

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Increased leukocyte apoptosis is intrinsically linked to disease patho-physiology, susceptibility to and severity of infections in type 2 diabetes mellitus (T2DM) patients. A consistent defect in neutrophil function is considered central to this increased risk for infections. Although redox imbalance is considered a potential mediator of these associated complications, detailed molecular evidence in clinical samples remains largely undetected. The study consisted of three groups (n = 50 each) of Asian Indians: early diagnosed diabetic patients, cases with late-onset diabetic complications and age and gender-matched healthy controls. We evaluated mitochondrial oxidative stress, levels of nuclear DNA damage and apoptosis in peripheral blood neutrophils isolated from T2DM patients. We observed that in both early and late diabetic subjects, the HbA1c levels in neutrophils were altered considerably with respect to healthy controls. Increased oxidative stress observed in both early and late diabetics imply the disentanglement of fine equilibrium of mitochondria-nuclear cross talk which eventually effected the augmentation of downstream nuclear cH2AX activation and caspase-3 expression. It would be overly naïve to refute the fact that mitochondrial deregulation in neutrophils perturbs immunological balance in type 2 diabetic conditions. By virtue of our data, we posit that maneuvering mitochondrial function might offer a prospective and viable method to modulate neutrophil function in T2DM. Nevertheless, similar investigations from other ethnic groups in conjunction with experimental evidences would be a preeminent need. Obviously, our study might aid to comprehend this complex interplay between mitochondrial dysfunction and neutrophil homeostasis in T2DM.

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“…Both resting neutrophils and those stimulated by phorbol 12-myristate 13-acetate (PMA) and zymosan from diabetic individuals produce more superoxide and have enhanced respiratory burst activities compared to those from healthy individuals. The increased oxidative respiratory burst activity in patients with diabetes may predispose to infection and lead to chronic inflammation [2]. In 2004, a new neutrophil-mediated defense mechanism, neutrophil extracellular traps (NETs), was reported.…”

Section: Neutrophilsmentioning

confidence: 99%

Reprogramming of metabolism in immune-mediated cells

Wada

2017

Diabetol Int

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Increased polymorphonuclear leukocyte respiratory burst function in type 2 diabetes

Cited by 49 publications

References 44 publications

Defects in Innate Immunity Predispose C57BL/6J-Lepr^db/Lepr^dbMice to Infection byStaphylococcus aureus

Defects in Innate Immunity Predispose C57BL/6J-Lepr^db/Lepr^dbMice to Infection byStaphylococcus aureus

Impairment of Mitochondrial–Nuclear Cross Talk in Neutrophils of Patients with Type 2 Diabetes Mellitus

Reprogramming of metabolism in immune-mediated cells

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Increased polymorphonuclear leukocyte respiratory burst function in type 2 diabetes

Cited by 49 publications

References 44 publications

Defects in Innate Immunity Predispose C57BL/6J-Leprdb/LeprdbMice to Infection byStaphylococcus aureus

Defects in Innate Immunity Predispose C57BL/6J-Leprdb/LeprdbMice to Infection byStaphylococcus aureus

Impairment of Mitochondrial–Nuclear Cross Talk in Neutrophils of Patients with Type 2 Diabetes Mellitus

Reprogramming of metabolism in immune-mediated cells

Contact Info

Product

Resources

About

Defects in Innate Immunity Predispose C57BL/6J-Lepr^db/Lepr^dbMice to Infection byStaphylococcus aureus

Defects in Innate Immunity Predispose C57BL/6J-Lepr^db/Lepr^dbMice to Infection byStaphylococcus aureus