Impairment of the oxygen-dependent microbicidal mechanisms of polymorphonuclear neutrophils in patients with type 2 diabetes is not associated with increased susceptibility to infection

Wykretowicz, Andrzej; Wierusz‐Wysocka, Bogna; Wysocki, Jan; Szczepanik, Adam; Wysocki, Henryk

doi:10.1016/0168-8227(93)90114-k

Cited by 26 publications

(21 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study provides unambiguous evidence that T1D patients have significantly lower serum MPO levels compared with controls. In support of our results, MPO activity was found to be lower in the neutrophils from T1D patients, an indication of impaired neutrophil function (45,46) and lower intracellular MPO of neutrophils was also observed in T2D patients (47). However, two previous studies with very small sample sizes (30 and 37 patients, respectively) found marginally higher plasma MPO levels in T1D patients compared with controls (48,49).…”

Section: Discussionsupporting

confidence: 76%

Discovery and Validation of Serum Protein Changes in Type 1 Diabetes Patients Using High Throughput Two Dimensional Liquid Chromatography-Mass Spectrometry and Immunoassays

Zhi

Sharma

Purohit

et al. 2011

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Type 1 diabetes (T1D) is expected to cause significant changes in the serum proteome; however, few studies have systematically assessed the proteomic profile change associated with the disease. In this study, a semiquantitative spectral counting-based two dimensional liquid chromatography mass spectrometry platform was used to analyze serum samples from T1D patients and controls. In this discovery phase, significant differences were found for 21 serum proteins implicated in inflammation, oxidation, metabolic regulation, and autoimmunity. To assess the validity of these findings, six candidate proteins including adiponectin, insulin-like growth factor binding protein 2, serum amyloid protein A, C-reactive protein, myeloperoxidase, and transforming growth factor beta induced were selected for subsequent immune assays for 1139 T1D patients and 848 controls. A series of statistical analyses using cases and controls matched for age, sex, and genetic risk confirmed that T1D patients have significantly higher serum levels for four of the six proteins: adiponectin (odds ratio (OR) ‫؍‬ 1.95, p ‫؍‬ 10 ؊27 ), insulin-like growth factor binding protein 2 (OR ‫؍‬ 2.02, p < 10 ؊20 ), C-reactive protein (OR ‫؍‬ 1.13, p ‫؍‬ 0.007), serum amyloid protein A (OR ‫؍‬ 1.51, p < 10 ؊16 ); whereas the serum levels were significantly lower in patients than controls for the two other proteins: transforming growth factor beta induced (OR ‫؍‬ 0.74, p < 10 ؊5 ) and myeloperoxidase (OR ‫؍‬ 0.51, p < 10 ؊41 ). Compared with subjects in the bottom quartile, subjects in the top quartile for adiponectin (OR ‫؍‬ 6.29, p < 10 ؊37 ), insulin-like growth factor binding protein 2 (OR ‫؍‬ 7.95, p < 10 ؊46 ), C-reactive protein (OR ‫؍‬ 1.38, p ‫؍‬ 0.025), serum amyloid protein A (OR ‫؍‬ 3.36, p < 10 ؊16 ) had the highest risk of T1D, whereas subjects in the top quartile of transforming growth factor beta induced (OR ‫؍‬ 0.41, p < 10 ؊11 ) and myeloperoxidase (OR ‫؍‬ 0.10, p < 10 ؊43

show abstract

Section: Discussionsupporting

confidence: 76%

Discovery and Validation of Serum Protein Changes in Type 1 Diabetes Patients Using High Throughput Two Dimensional Liquid Chromatography-Mass Spectrometry and Immunoassays

Zhi

Sharma

Purohit

et al. 2011

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…Neutrophils recovered from patients with type 2 diabetes have been shown to exhibit impaired bactericidal activity (6,15,41,48). To determine whether leukocytes from db/db mice would show a similar defect, we performed S. aureus killing assays with mouse blood.…”

Section: Functional Analyses Of Blood Leukocytesmentioning

confidence: 99%

“…A consistent defect in the humoral or cell-mediated host immune system of diabetic patients has not been demonstrated. However, deficiencies in the host innate immune response are apparent since clinical investigations have indicated that phagocytes from type 2 diabetic patients are in a heightened state of oxidative stress and have impaired bactericidal activity and chemotaxis (6,15,41,48). Clearly, numerous pathophysiologic perturbations contribute to the recurrence of soft tissue and bone infections in the lower extremity of patients with diabetes.…”

mentioning

confidence: 99%

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

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

“…The investigators have found that MPO activity in neutrophils of patients with DM was lower than controls (p< 0.05). Wykretowicz et al (2) have shown that intracellular killing activity and MPO activity of the PMNs in patients with DM sinificantly decreased (p<0.01, p<0.01). The researchers have claimed that the hyperglycemia seems to be one of the most likely cause of the observed disturbances.…”

Section: Discussionmentioning

confidence: 97%

“…It is known that PMN functions are deteriorated in type 2 diabetes mellitus (T2DM) patients; thus, they become more susceptible against infections. The deterioration of PMN functions, expecially the decrease in their intracellular killing activity of these patients was demonstrated by several studies (1,2).…”

Section: Introductionmentioning

confidence: 94%

The effect of some antibiotics on polymorphonuclear leukocyte (PMN) functions and PMN&#8217;s myeloperoxidase activity, glutathione and malondialdehyde levels of patients with type 2 Diabetes melliitus in vitro

Rayaman

Çevikbaş

et al. 2013

MUSBED

View full text Add to dashboard Cite

Bazı antibiyotiklerin Tip 2 diabetes mellitus'lu hastaların polimorfonüklear lökosit (PNL) fonksiyonları ve PNL'lerin miyeloperoksidaz aktivitesi, glutatyon ile malondialdehit düzeyleri üzerine in vitro etkisi Amaç: Çalışmamızda diabetes mellitus (DM)'lu hastaların polimorf nüveli lökosit (PNL) fonksiyonları ile sağlıklı gönüllülerin miyeloperoksidaz (MPO) aktivitesi, glutatyon (GSH) ve malondialdehit (MDA) düzeylerini karşılaştırıp arasındaki ilişkiyi saptamayı amaçladık. Bunun yanında siprofloksasin, rifampisin ve doksisiklinin PNL fonksiyonları, MPO aktivitesi ve GSH ile MDA düzeyleri üzerine immunomodülatör etkilerini araştırdık. Yöntemler: Çalışmamızda Tip 2 diyabeti olan 13 hasta ve 13 sağlıklı gönüllü yer almaktadır. Antibiyotiklerin PNL fonksiyonları üzerine olan etkileri in vitro koşullarda araştırıldı. PNL'ler (1x10 7 hücre/ml) venöz kandan Ficoll-hypaque gradient santrifügasyon metodu kullanılarak izole edildi. PNL'lerin MPO aktivitesi modifiye O-dianisidin yöntemi, GSH miktarı Ellman yöntemi ve MDA düzeyleri ise Beuge yöntemi kullanılarak belirlendi. Bulgular: DM'lu hasta PNL'lerinin fagositik (p<0.05) ve hücre içi öldürme aktivitesi (p<0.01) sağlıklı gönüllülere göre anlamlı olarak azaldı. Siprofloksasin sağlıklı gönüllü ve tüm hasta PNL'lerinin fagositik ve hücre içi öldürme aktivitesini kontrol değerlere göre anlamlı olarak artırdı (p<0.01 ve p<0.01). Rifampisin, DM'lu hasta PNL'lerinin hücre içi öldürme aktivitesini anlamlı olarak artırdı (p<0.05). Rifampisin ve doksisiklin ise, sağlıklı gönüllü PNL'lerinin fagositik ve hücre içi öldürme aktivitesini kontrol değerlerine göre anlamlı olarak azalttı (p<0.05). Siprofloksasin (2.5 μg/ml) sağlıklı gönüllülerin (p<0.01) ve hastaların MPO aktivitesini ve MDA düzeyini ilaçsız kontrole göre anlamlı olarak artırdı (p<0.01). Ancak aynı ilaç DM'lu hasta PNL'lerinin GSH düzeyini anlamlı olarak azalttı (p<0.05). Sonuçlar: İmmün sistemi bozulmuş Tip 2 DM'lu hastalardaki ve sağlıklı gönüllerdeki MPO aktivitesi ile PNL fonksiyonları arasındaki ilişkinin önemi siprofloksasin ile hücresel immün sistemin desteklenmesi ve PNL'lerin MPO aktivitesi ile beraber PNL aktivitelerinin artışı ile gösterildi. Anahtar sözcükler: Diabetes mellitus, miyeloperoksidaz, fagositoz, hücre içi öldürme aktivitesi, antibiyotikler ABS TRACTThe effect of some antibiotics on polymorphonuclear leukocyte (PMN) functions and PMN's myeloperoxidase activity, glutathione and malondialdehyde levels of patients with type 2 diabetes mellitus in vitro Objective: In this study, our objective was to compare PMN functions and myeloperoxidase (MPO) activity, glutathione (GSH) and malondialdehyde (MDA) levels and assess the relationship between PMN functions and enzyme levels in patients with type 2 diabetes mellitus (T2DM) and healthy volunteers. We also examined the immunomodulatory effects of ciprofloxacin, rifampicine and doxycycline on PMN functions, MPO activity and GSH and MDA levels. Methods: Thirteen patients with T2DM and 13 healthy volunteers were included in the study. The effect of antibiotic...

show abstract

Impairment of the oxygen-dependent microbicidal mechanisms of polymorphonuclear neutrophils in patients with type 2 diabetes is not associated with increased susceptibility to infection

Cited by 26 publications

References 14 publications

Discovery and Validation of Serum Protein Changes in Type 1 Diabetes Patients Using High Throughput Two Dimensional Liquid Chromatography-Mass Spectrometry and Immunoassays

Discovery and Validation of Serum Protein Changes in Type 1 Diabetes Patients Using High Throughput Two Dimensional Liquid Chromatography-Mass Spectrometry and Immunoassays

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

The effect of some antibiotics on polymorphonuclear leukocyte (PMN) functions and PMN&#8217;s myeloperoxidase activity, glutathione and malondialdehyde levels of patients with type 2 Diabetes melliitus in vitro

Contact Info

Product

Resources

About

Impairment of the oxygen-dependent microbicidal mechanisms of polymorphonuclear neutrophils in patients with type 2 diabetes is not associated with increased susceptibility to infection

Cited by 26 publications

References 14 publications

Discovery and Validation of Serum Protein Changes in Type 1 Diabetes Patients Using High Throughput Two Dimensional Liquid Chromatography-Mass Spectrometry and Immunoassays

Discovery and Validation of Serum Protein Changes in Type 1 Diabetes Patients Using High Throughput Two Dimensional Liquid Chromatography-Mass Spectrometry and Immunoassays

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

The effect of some antibiotics on polymorphonuclear leukocyte (PMN) functions and PMN&amp;#8217;s myeloperoxidase activity, glutathione and malondialdehyde levels of patients with type 2 Diabetes melliitus in vitro

Contact Info

Product

Resources

About

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

The effect of some antibiotics on polymorphonuclear leukocyte (PMN) functions and PMN’s myeloperoxidase activity, glutathione and malondialdehyde levels of patients with type 2 Diabetes melliitus in vitro