Neutrophil extracellular traps contain mitochondrial as well as nuclear DNA and exhibit inflammatory potential

Cytometry. Part A : the journal of the International Society for Analytical Cytology - Tập 81A Số 3 - Trang 238-247 - 2012
Ravi S. Keshari1, Anupam Jyoti1, Sachin Kumar1, Megha Dubey1, Anupam Verma2, Bangalore Suresh Srinag3, Hanumanthappa Krishnamurthy3, Manoj Kumar Barthwal1, Madhu Dikshit1
1Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226 001, India
2Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
3Central Image-Flow Facility, National Centre for Biological Sciences, Bangalore, India

Tóm tắt

AbstractNeutrophils expel extracellular traps (NETs) to entrap and exterminate the invaded micro‐organisms. Acute/chronic inflammatory disorders are often observed with aberrantly enhanced NETs formation and high nitric oxide (NO) availability. Recent study from this laboratory demonstrated release of NETs from human neutrophils following treatment with SNP or SNAP. This study is an extension of our previous finding to explore the extracellular bacterial killing, source of DNA in the expelled NETs, their ability to induce proinflammatory cytokines release from platelets/THP‐1 cells, and assessment of NO‐mediated free radical formation by using a consistent NO donor, DETA‐NONOate. NO‐mediated NETs exhibited extracellular bacterial killing as determined by colony forming units. NO‐mediated NETs formation was due to the activation of NADPH oxidase and myeloperoxidase. NO‐ or PMA‐mediated NETs were positive for both nuclear and mitochondrial DNA as well as proteolytic enzymes. Incubation of NETs with human platelets enhanced the release of IL‐1β and IL‐8, while with THP‐1 cells, release of IL‐1β, IL‐8, and TNFα was observed. This study demonstrates that NO by augmenting enzymatic free radical generation release NETs to promote extracellular bacterial killing. These NETs were made up of mitochondrial and nuclear DNA and potentiated release of proinflammatory cytokines. © 2011 International Society for Advancement of Cytometry

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Cytometry. Part A : the journal of the International Society for Analytical Cytology

Tập 81A Số 3

238-247

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