This document summarizes information on neutrophils and neutrophil extracellular traps (NETs). Neutrophils are white blood cells that protect the body from infection through phagocytosis and release of reactive oxygen species and antimicrobial peptides. NETs are networks of DNA released by neutrophils that trap and kill pathogens. NET formation, or NETosis, can be triggered by microbes, cytokines, and toxins. NETosis plays a role in diseases like thrombosis, lung diseases, and COVID-19. Snake venom toxins and UV radiation can also induce NETosis. Potential therapies target NETosis through inhibitors of neutrophil elastase and microtuble formation or use of recombinant DNAse.

1. Presented By:
P.Hari Chander Reddy
RT/2021/609
Department of Regulatory
Toxicology.
Guided By:
DR.Chandraiah Godugu.
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2. CONTENTS:
INFLAMMATION
NEUTROPHILLS
FUNCTIONS OF NEUTROPHILS
NEUTROPHIL EXTRACELLULAR TRAPS (NET)
NETosis
MECHANISMS OF NETosis
NETOSIS ROLE IN PATHOLOGICAL AND TOXICOLOGICAL CONDITIONS.
THERAPHY FOR NETOSIS
CONCLUSION
REFERENCES
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3. INFLAMMATION:
• Inflammation is a response triggered by noxious stimuli and
conditions such as Infection and Tissue injury
PROCESS OF INFLAMMATION
TRIGGERING
MIGRATING
KILLING
RESOLUTION
TISSUE REPAIR
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4. Mechanism of Inflammation:
Inflammation and tissue repair @ LEGGER ID 62002173
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5. Neutrophil:
• Neutrophils are a type of white blood cells that protect us from
infections.
• They make up approximately 40 to 60% of the white blood cells in our
bodies.
• These are Professional phagocytes contain a huge amount of
bactericidal weaponry in their granules that allows to destroy the
pathogen in the process of phagocytosis.
• Neutrophiles are short lived, in blood they survive up to 8 hours and
in tissues up to 7 days
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6. Functions of Neutrophil:
Phagocytosis.
ROS
generation.
Degranulation.
Neutrophil
Extracellular
Trap.
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7. CONT....
https://doi.org/10.3389/fimmu.2019.02507
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8. NEUTROPHIL
EXTRACELLULAR
TRAPS:
 NET’s are meshes of DNA
decorated with anti-
microbial peptides that are
released by neutrophil's in
response to various stimuli.
 Pathogens (yeast, bacteria)
stick to the DNA fibrils that
prevents them from
spreading in to the tissue
and further degraded by
granule proteins that are
attached to the chromatin
network.
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9. COMPONENTS OF NET’S:
Nuclear components- DNA,
Histones.
Granular components-
Myeloperoxidase, Cathepsin
G, Neutrophillic elastase,
Lysosymes, Lactoferin,
Cytoplasmic components-
Calprotectin.
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10. NETosis
Infographic: How Neutrophil Extracellular Traps Work | The Scientist Magazine® (the-scientist.com)
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11. TRIGGERS FOR NETOSIS:
MICROORGANISMS
Aspergillus fumigatus
Candida albicans
Cryptococcus
Escherichia coli
Mycobacterium tuberclosis
Staphyloccocus aureus
Haemophilus influenzae
HIV virus
OTHERS
Proinflammatory cytokines.
Platelets
Lipopolysaccaride(LPS) protein.
Phorbol-12-myristate 13- acetate (PMA)
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12. MECHANISMS OF NET FORMATION :
SUISIDAL NETosis:
VITAL NETosis
Front. Immunol., 02 December 2020 | https://doi.org/10.3389/fimmu.2020.610696
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13. Citrullination:
www.omicsonline.org%2farticles-images%2f2155-9899-4-146-g002.
https://www.researchgate.net/journal/International-Journal-of-
Molecular-Sciences-1422-0067
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14. ROLE OF NETosis IN PATHOLOGICAL
CONDITIONS:
www.researchgate.net.
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15. CONT...
THROMBOSIS
PULMONARY DISEASES
CYSTIC FIBROSIS
COVID-19
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16. ROLE OF NETosis
IN TOXIC
CONDITIONS:
ECHIS CARINATUS SNAKE BITE
https://r.search.yahoo.com.
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17. SNAKE VENOM
TOXINS.
E.Carnitis venom is a procoagulant,
NETS also promotes clot formation.
Blood vessel remains blocked.
Prevents entry of venom in to
circulation.
Accumlation.
Loss of ECM integrity.
SVMPS- Snake venom
metalloproteinases
SVHYS- Snake venom
Hyaluronidases
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18. UV RADIATION
EXTRACELLULAR RELEASE OF TRAPS
GRANULAR COMPONENTS DIFFUSE IN TO NUCLEUS.
ROS GENERATION
ACTIVATION OF NADPH OXIDASES
TRIGGERING STIMULI FOR NEUTROPHILS
IRRADIATION OF SKIN
Photoaging symptoms
• Irregular
pigmentation
• Deep wrinkles.
• Dryness
• Elastosis
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19. THERAPY FOR NETosis:
Anti-cytokine therapy: Recombinant Anakinra. Currently undergoing
clinical trials to treat cov-19.
(https://clinicaltrials.gov: NCT04324021, NCT04330638, NCT0273570
7).
NE Inhibitors: Sivelestat.
 Microtuble inhibitor: Colchicine.
Recombinant DNAse 1: PRX-110.
(https://clinicaltrials.gov: NCT02605590, NCT02722122)
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20. CONCLUSION
Signaling mechanisms and process of chromatin modification and
decondensation remains unclear.
No sufficient evidence to support NETosis in pathogenesis of many
diseases.
 In vital NETosis structure and formation of vesicles need to be
investigated.
Which stimuli can induce NETosis and which proteins can inhibit NET
formation.
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21. REFERENCES
1- Origin and physiological roles of inflammation https://doi.org/10.1038/nature07201.
2- The Neutrophil’s Choice: Phagocytose vs Make Neutrophil Extracellular
Trapshttps://dx.doi.org/10.3389%2Ffimmu.2018.00288.
3- The Regulatory Effects of Interleukin-4 Receptor Signaling on Neutrophils in Type 2 Immune
Responses. https://doi.org/10.3389/fimmu.2019.02507.
4-Front. Immunol., 02 December 2020 | https://doi.org/10.3389/fimmu.2020.610696.
5- NETosis: Molecular Mechanisms, Role in Physiology and Pathology.
https://dx.doi.org/10.1134%2FS0006297920100065.
6- Yipp BG, Kubes P. NETosis: how vital is it? Blood. 2013 Oct 17;122(16):2784-94. doi:
10.1182/blood-2013-04-457671. Epub 2013 Sep 5. PMID: 24009232.
7- The Emerging Role of Neutrophil Extracellular Traps in Respiratory Disease
https://doi.org/10.1016/j.chest.2019.06.012.
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22. CONT…
8- Zuo, Y., Yalavarthi, S., Shi, H., Gockman, K., Zuo, M., Madison, J. A., Blair, C., Weber, A.,
Barnes, B. J., Egeblad, M., Woods, R. J., Kanthi, Y., & Knight, J. S. (2020). Neutrophil
extracellular traps in COVID-19. JCI insight, 5(11), e138999.
https://doi.org/10.1172/jci.insight.138999.
9- Lack of DNase activity are key factors in Echis carinatus venom-induced tissue
destruction. doi: 10.1038/ncomms11361. PMID: 27093631; PMCID: PMC4838891.
10- Zawrotniak M, Bartnicka D, Rapala-Kozik M. UVA and UVB radiation induce the
formation of neutrophil extracellular traps by human polymorphonuclear cells. J Photochem
Photobiol B. 2019 Jul;196:111511. doi: 10.1016/j.jphotobiol.2019.111511. Epub 2019 May
16. PMID: 31129510.
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23. Prof. Arturo Zychlinsky, PhD
Scientific member (Director)
Cellular Microbiology
Max Planck Institute for Infection
Biology
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