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      Neutrophil extracellular traps in central nervous system pathologies: A mini review

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          Abstract

          Neutrophils are the first cells to be recruited to sites of acute inflammation and contribute to host defense through phagocytosis, degranulation and neutrophil extracellular traps (NETs). Neutrophils are rarely found in the brain because of the highly selective blood-brain barrier (BBB). However, several diseases disrupt the BBB and cause neuroinflammation. In this regard, neutrophils and NETs have been visualized in the brain after various insults, including traumatic (traumatic brain injury and spinal cord injury), infectious (bacterial meningitis), vascular (ischemic stroke), autoimmune (systemic lupus erythematosus), neurodegenerative (multiple sclerosis and Alzheimer’s disease), and neoplastic (glioma) causes. Significantly, preventing neutrophil trafficking into the central nervous system or NET production in these diseases alleviates brain pathology and improves neurocognitive outcomes. This review summarizes the major studies on the contribution of NETs to central nervous system (CNS) disorders.

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          Most cited references155

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          Neutrophil extracellular traps kill bacteria.

          Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome. Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria. These neutrophil extracellular traps (NETs) degrade virulence factors and kill bacteria. NETs are abundant in vivo in experimental dysentery and spontaneous human appendicitis, two examples of acute inflammation. NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria.
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            Neutrophil extracellular traps in immunity and disease

            Neutrophils are innate immune phagocytes that have a central role in immune defence. Our understanding of the role of neutrophils in pathogen clearance, immune regulation and disease pathology has advanced dramatically in recent years. Web-like chromatin structures known as neutrophil extracellular traps (NETs) have been at the forefront of this renewed interest in neutrophil biology. The identification of molecules that modulate the release of NETs has helped to refine our view of the role of NETs in immune protection, inflammatory and autoimmune diseases and cancer. Here, I discuss the key findings and concepts that have thus far shaped the field of NET biology.
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              Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood.

              It has been known for many years that neutrophils and platelets participate in the pathogenesis of severe sepsis, but the inter-relationship between these players is completely unknown. We report several cellular events that led to enhanced trapping of bacteria in blood vessels: platelet TLR4 detected TLR4 ligands in blood and induced platelet binding to adherent neutrophils. This led to robust neutrophil activation and formation of neutrophil extracellular traps (NETs). Plasma from severely septic humans also induced TLR4-dependent platelet-neutrophil interactions, leading to the production of NETs. The NETs retained their integrity under flow conditions and ensnared bacteria within the vasculature. The entire event occurred primarily in the liver sinusoids and pulmonary capillaries, where NETs have the greatest capacity for bacterial trapping. We propose that platelet TLR4 is a threshold switch for this new bacterial trapping mechanism in severe sepsis.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                17 February 2023
                2023
                : 10
                : 1083242
                Affiliations
                College of Medicine, Alfaisal University , Riyadh, Saudi Arabia
                Author notes

                Edited by: Ahmet Emre Eskazan, Istanbul University-Cerrahpaşa, Türkiye

                Reviewed by: Abbas Azadmehr, Babol University of Medical Sciences, Iran; Tetyana Chumak, University of Gothenburg, Sweden

                *Correspondence: Saleha Abdul Rab, sabdulrab@ 123456alfaisal.edu

                These authors share first authorship

                This article was submitted to Hematology, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2023.1083242
                9981681
                36873885
                a4567e37-80b8-4e54-bc41-e8f2ca9fc933
                Copyright © 2023 Shafqat, Noor Eddin, Adi, Al-Rimawi, Abdul Rab, Abu-Shaar, Adi, Alkattan and Yaqinuddin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 October 2022
                : 06 February 2023
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 155, Pages: 10, Words: 8691
                Categories
                Medicine
                Mini Review

                neutrophil extracellular traps,blood-brain barrier,neuroinflammation,stroke,neurodegeneration,traumatic brain injury,alzheimer’s disease,neutrophils (pmns)

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