Elevated homocysteine levels in type 2 diabetes induce constitutive neutrophil extracellular traps

Constitutively active neutrophil extracellular traps (NETs) and elevated plasma homocysteine are independent risk factors for Type 2 Diabetes (T2D) associated vascular diseases. Here, we show robust NETosis due to elevated plasma homocysteine levels in T2D subjects and increased components of NETs s...

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Bibliographic Details
Published in:Scientific reports 2016-11, Vol.6 (1), p.36362-36362, Article 36362
Main Authors: Joshi, Manjunath B, Baipadithaya, Guruprasad, Balakrishnan, Aswath, Hegde, Mangala, Vohra, Manik, Ahamed, Rayees, Nagri, Shivashankara K, Ramachandra, Lingadakai, Satyamoorthy, Kapaettu
Format: Article
Language:English
Subjects:
631/250/2504
631/250/262
Blood Platelets - metabolism
Calcium (mitochondrial)
Calcium - metabolism
Cell-Free Nucleic Acids - blood
Deoxyribonucleic acid
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
DNA
Elastase
Extracellular Traps - metabolism
Female
Health risk assessment
Homeostasis
Homocysteine
Homocysteine - blood
Humanities and Social Sciences
Humans
Immune response
Interleukin 6
Leukocyte Elastase - metabolism
Leukocytes (neutrophilic)
Male
Middle Aged
Mitochondria
multidisciplinary
NAD(P)H oxidase
NADPH Oxidases - metabolism
Neutrophils
Neutrophils - metabolism
Platelet aggregation
Risk factors
Science
Up-Regulation
Vascular diseases
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Summary:Constitutively active neutrophil extracellular traps (NETs) and elevated plasma homocysteine are independent risk factors for Type 2 Diabetes (T2D) associated vascular diseases. Here, we show robust NETosis due to elevated plasma homocysteine levels in T2D subjects and increased components of NETs such as neutrophil elastase and cell free DNA. Cooperative NETs formation was observed in neutrophils exposed to homocysteine, IL-6 and high glucose suggesting acute temporal changes tightly regulate constitutive NETosis. Homocysteine induced NETs by NADPH oxidase dependent and independent mechanisms. Constitutively higher levels of calcium and mitochondrial superoxides under hyperglycemic conditions were further elevated in response to homocysteine leading to accelerated NETosis. Homocysteine showed robust interaction between neutrophils and platelets by inducing platelet aggregation and NETosis in an interdependent manner. Our data demonstrates that homocysteine can alter innate immune function by promoting NETs formation and disturbs homeostasis between platelets and neutrophils which may lead to T2D associated vascular diseases.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep36362