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

Manjunath B. Joshi, Guruprasad Baipadithaya, Aswath Balakrishnan, Mangala Hegde, Manik Vohra, Rayees Ahamed, Shivashankara K. Nagri, Lingadakai Ramachandra, Kapaettu Satyamoorthy

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number36362
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 04-11-2016

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Homocysteine
Type 2 Diabetes Mellitus
Neutrophils
Vascular Diseases
Blood Platelets
Leukocyte Elastase
NADPH Oxidase
Extracellular Traps
Platelet Aggregation
Superoxides
Interleukin-6
Homeostasis
Calcium
Glucose
DNA

All Science Journal Classification (ASJC) codes

  • General

Cite this

Joshi, Manjunath B. ; Baipadithaya, Guruprasad ; Balakrishnan, Aswath ; Hegde, Mangala ; Vohra, Manik ; Ahamed, Rayees ; Nagri, Shivashankara K. ; Ramachandra, Lingadakai ; Satyamoorthy, Kapaettu. / Elevated homocysteine levels in type 2 diabetes induce constitutive neutrophil extracellular traps. In: Scientific Reports. 2016 ; Vol. 6.
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abstract = "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.",
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Joshi, MB, Baipadithaya, G, Balakrishnan, A, Hegde, M, Vohra, M, Ahamed, R, Nagri, SK, Ramachandra, L & Satyamoorthy, K 2016, 'Elevated homocysteine levels in type 2 diabetes induce constitutive neutrophil extracellular traps', Scientific Reports, vol. 6, 36362. https://doi.org/10.1038/srep36362

Elevated homocysteine levels in type 2 diabetes induce constitutive neutrophil extracellular traps. / Joshi, Manjunath B.; Baipadithaya, Guruprasad; Balakrishnan, Aswath; Hegde, Mangala; Vohra, Manik; Ahamed, Rayees; Nagri, Shivashankara K.; Ramachandra, Lingadakai; Satyamoorthy, Kapaettu.

In: Scientific Reports, Vol. 6, 36362, 04.11.2016.

Research output: Contribution to journalArticle

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AU - Joshi, Manjunath B.

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AU - Hegde, Mangala

AU - Vohra, Manik

AU - Ahamed, Rayees

AU - Nagri, Shivashankara K.

AU - Ramachandra, Lingadakai

AU - Satyamoorthy, Kapaettu

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N2 - 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.

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