Elevated Homocysteine Levels in Type 2 Diabetes induce Constitutive Neutrophil Extracellular Traps

Joshi, Manjunath B and Baipadithaya, Guruprasad and Balakrishnan, Aswath and Hegde, Mangala and Vohra, Manik and Ahamed, Rayees and Nagri, Shivashankara K and Ramachandra, L and Satyamoorthy, K (2016) Elevated Homocysteine Levels in Type 2 Diabetes induce Constitutive Neutrophil Extracellular Traps. Scientific Reports, 6 (11). pp. 1-15.

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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.

Item Type: Article
Subjects: Life Sciences > MLSC Manipal
Medicine > KMC Manipal > Medicine
Medicine > KMC Manipal > Surgery
Depositing User: KMC Library
Date Deposited: 23 Nov 2016 09:10
Last Modified: 23 Nov 2016 09:10
URI: http://eprints.manipal.edu/id/eprint/147592

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