ArticleShock (Augusta, Ga.)2015
Inhibition of Neutrophils by Hypertonic Saline Involves Pannexin-1, CD39, CD73, and Other Ectonucleotidases.
Article in Shock (Augusta, Ga.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Should Hypertonic Saline Be Considered for the Treatment of Intracranial Hypertension? A Review of Current Evidence and Clinical Practices.Korean journal of neurotrauma · 2024Review
- Upregulation of CD39 During Gout Attacks Promotes Spontaneous Remission of Acute Gouty Inflammation.Inflammation · 2024Article
- Adenosine metabolized from extracellular ATP ameliorates organ injury by triggering ARespiratory research · 2023Article
- Soluble uric acid inhibits β2 integrin-mediated neutrophil recruitment in innate immunity.Blood · 2022Article
- Hypertonic Solution in Severe COVID-19 Patient: A Potential Adjuvant Therapy.Frontiers in medicine · 2022Review
- Pannexin1: Role as a Sensor to Injury Is Attenuated in Pretype 2 Corneal Diabetic Epithelium.Analytical cellular pathology (Amsterdam) · 2021Article
- Ectonucleotidases in Acute and Chronic Inflammation.Frontiers in pharmacology · 2020Review
- ATP amplifies NADPH-dependent and -independent neutrophil extracellular trap formation.Scientific reports · 2019Article
- Exciting and not so exciting roles of pannexins.Neuroscience letters · 2019Review
- Sustained Ca2+ mobilizations: A quantitative approach to predict their importance in cell-cell communication and wound healing.PloS one · 2019Article
- Mechanisms of ATP Release by Inflammatory Cells.International journal of molecular sciences · 2018Review
- The role of connexin and pannexin containing channels in the innate and acquired immune response.Biochimica et biophysica acta. Biomembranes · 2018Review
- Cell culture: complications due to mechanical release of ATP and activation of purinoceptors.Cell and tissue research · 2017Review
- Complement C5a-Induced Changes in Neutrophil Morphology During Inflammation.Scandinavian journal of immunology · 2017Article
- Purinergic Signaling and the Immune Response in Sepsis: A Review.Clinical therapeutics · 2016Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypertonic saline (HS) resuscitation has been studied as a possible strategy to reduce polymorphonuclear neutrophil (PMN) activation and tissue damage in trauma patients. Hypertonic saline blocks PMNs by adenosine triphosphate (ATP) release and stimulation of A2a adenosine receptors. Here, we studied the underlying mechanisms in search of possible reasons for the inconsistent results of recent clinical trials with HS resuscitation. Purified human PMNs or PMNs in whole blood were treated with HS to simulate hypertonicity levels found after HS resuscitation (40 mmol/L beyond isotonic levels). Adenosine triphosphate release was measured with a luciferase assay. Polymorphonuclear neutrophil activation was assessed by measuring oxidative burst. The pannexin-1 (panx1) inhibitor panx1 and the gap junction inhibitor carbenoxolone (CBX) blocked ATP release from PMNs in purified and whole blood preparations, indicating that HS releases ATP via panx1 and gap junction channels. Hypertonic saline blocked N-formyl-Met-Leu-Phe-induced PMN activation by 40% in purified PMN preparations and by 60% in whole blood. These inhibitory effects were abolished by panx1 but only partially reduced by CBX, which indicates that panx1 has a central role in the immunomodulatory effects of HS. Inhibition of the ectonucleotidases CD39 and CD73 abolished the suppressive effect of HS on purified PMN cultures but only partially reduced the effect of HS in whole blood. These findings suggest redundant mechanisms in whole blood that may strengthen the immunomodulatory effect of HS in vivo. We conclude that HS resuscitation exerts anti-inflammatory effects that involve panx1, CD39, CD73, and other ectonucleotidases, which produce the adenosine that blocks PMNs by stimulating their A2a receptors. Our findings shed new light on the immunomodulatory mechanisms of HS and suggest possible new strategies to improve the clinical efficacy of hypertonic resuscitation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.