Special Issue "Cellular and Molecular Mechanisms of Anaphylaxis: Lessons from Animal Models"

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: 30 April 2023 | Viewed by 3694

Special Issue Editors

Prof. Dr. Abdelouahab Bellou
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Guest Editor
1. Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA
2. Institute of Sciences in Emergency Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Interests: emergency medicine; hospital and emergency department designing; geriatric emergency medicine; critical care; physiology; immunology; shocks; quality and safety
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Paul Michel Mertès
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Guest Editor
Anaesthesia, Intensive Care and Perioperative Medicine, Nouvel Hôpital, Civil, Strasbourg University Hospital, 67000 Strasbourg, France
Interests: allergy; immunology; physiology; pharmacology; genomic; emergency medicine; animal models; anaesthesiology, critical care

Special Issue Information

Dear Colleagues,

The pathophysiological mechanisms of anaphylaxis are still under investigation. Despite intensive research produced by different groups at the international level, these mechanisms are still poorly understood. The role of pre-formed and neo-formed mediators in the onset of anaphylactic shock has been well explored, but their involvement at the cellular level remains to be clearly defined. The primum movens for the onset of anaphylaxis is an intense vasodilation responsible for the onset of shock and then respiratory and cardiac damage responsible for death with multiorgan dysfunction in very severe clinical manifestation.

Histamine is the main preformed mediator responsible for the occurrence of bronchospasm induced by bronchoconstriction leading to severe acute asthma responsible for acute respiratory failure. It is also responsible for vasodilation through stimulation of intracellular adenylate cyclase activating nitric oxide (NO) synthase leading to the production of NO, a potent vasodilator. However, our previous results do not confirm the benefit of inhibitors of NOS on anaphylactic shock published by other groups. In this Special Issue, a detailed focus on the current knowledge of the role of NO is proposed. The role of prostaglandins and leukotrienes, mediators neo-formed from the cellular membrane is suspected in the occurrence of anaphylactic shock. Our group recently showed that voltage-dependent potassium channels are probably involved in the onset of vasodilation responsible for anaphylactic shock. The role of another potent vasodilator mediator, hydrogen disulfide (H2S), remains to be demonstrated. In this Special Issue, we propose the presentation of our promising results on the inhibition of enzymes producing H2S which restores blood pressure. The mechanisms of hypovolemia linked to plasma transudation by disruption of cell junctions will also be discussed. Finally, the genomic mechanisms of the production of many mediators will be discussed in a systematic review of the literature.

Prof. Dr. Abdelouahab Bellou
Prof. Dr. Paul Michel Mertès
Guest Editors

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Keywords

  • anaphylaxis
  • allergy
  • immunology
  • emergency medicine
  • animal models

Published Papers (3 papers)

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Article
Combined Treatment with KV Channel Inhibitor 4-Aminopyridine and either γ-Cystathionine Lyase Inhibitor β-Cyanoalanine or Epinephrine Restores Blood Pressure, and Improves Survival in the Wistar Rat Model of Anaphylactic Shock
Biology 2022, 11(10), 1455; https://doi.org/10.3390/biology11101455 - 03 Oct 2022
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Abstract
The mechanism of anaphylactic shock (AS) remains incompletely understood. The potassium channel blocker 4-aminopyridine (4-AP), the inhibitors of cystathionine γ-lyase (ICSE), dl-propargylglycine (DPG) or β-cyanoalanine (BCA), and the nitric oxide (NO) synthase produce vasoconstriction and could be an alternative for the treatment of [...] Read more.
The mechanism of anaphylactic shock (AS) remains incompletely understood. The potassium channel blocker 4-aminopyridine (4-AP), the inhibitors of cystathionine γ-lyase (ICSE), dl-propargylglycine (DPG) or β-cyanoalanine (BCA), and the nitric oxide (NO) synthase produce vasoconstriction and could be an alternative for the treatment of AS. The aim of this study was to demonstrate the ability of L-NAME, ICSE alone or in combination with 4-AP to restore blood pressure (BP) and improve survival in ovalbumin (OVA) rats AS. Experimental groups included non-sensitized Wistar rats (n = 6); AS (n = 6); AS (n = 10 per group) treated i.v. with 4-AP (AS+4-AP), epinephrine (AS+EPI), AS+DPG, AS+BCA, or with L-NAME (AS+L-NAME); or AS treated with drug combinations 4-AP+DPG, 4-AP+BCA, 4-AP+L-NAME, or 4-AP+EPI. AS was induced by i.v. OVA (1 mg). Treatments were administered i.v. one minute after AS induction. Mean arterial BP (MAP), heart rate (HR), and survival were monitored for 60 min. Plasma levels of histamine, prostaglandin E2 (PGE2) and F2 (PGF2α), leukotriene B4 and C4, angiotensin II, vasopressin, oxidative stress markers, pH, HCO3, PaO2, PaCO2, and K+ were measured. OVA induced severe hypotension and all AS rats died. Moreover, 4-AP, 4-AP+EPI, or 4-AP+BCA normalized both MAP and HR and increased survival. All sensitized rats treated with 4-AP alone or with 4-AP+BCA survived. The time-integrated MAP “area under the curve” was significantly higher after combined 4-AP treatment with ICSE. Metabolic acidosis was not rescued and NO, ICSE, and Kv inhibitors differentially alter oxidative stress and plasma levels of anaphylactic mediators. The AS-induced reduction of serum angiotensin II levels was prevented by 4-AP treatment alone or in combination with other drugs. Further, 4-AP treatment combined with EPI or with BCA also increased serum PGF2α, whereas only the 4-AP+EPI combination increased serum LTB4. Serum vasopressin and angiotensin II levels were increased by 4-AP treatment alone or in combination with other drugs. Moreover, 4-AP alone and in combination with inhibition of cystathionine γ-lyase or EPI normalizes BP, increases serum vasoconstrictor levels, and improves survival in the Wistar rat model of AS. These findings suggest possible investigative treatment pathways for research into epinephrine-refractory anaphylactic shock in patients. Full article
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Article
Impaired Myocardial Mitochondrial Function in an Experimental Model of Anaphylactic Shock
Biology 2022, 11(5), 730; https://doi.org/10.3390/biology11050730 - 10 May 2022
Cited by 1 | Viewed by 887
Abstract
Anaphylactic shock (AS) is associated with a profound vasodilation and cardiac dysfunction. The cellular mechanisms underlying AS-related cardiac dysfunction are unknown. We hypothesized that myocardial mitochondrial dysfunction may be associated with AS cardiac dysfunction. In controls and sensitized Brown Norway rats, shock was [...] Read more.
Anaphylactic shock (AS) is associated with a profound vasodilation and cardiac dysfunction. The cellular mechanisms underlying AS-related cardiac dysfunction are unknown. We hypothesized that myocardial mitochondrial dysfunction may be associated with AS cardiac dysfunction. In controls and sensitized Brown Norway rats, shock was induced by ovalbumin i.v bolus, and abdominal aortic blood flow (ABF), systemic mean arterial pressure (MAP), and lactatemia were measured for 15 min. Myocardial mitochondrial function was assessed with the evaluation of mitochondrial respiration, oxidative stress production by reactive oxygen species (ROS), reactive nitrogen species (RNS), and the measurement of superoxide dismutases (SODs) activity. Oxidative damage was assessed by lipid peroxidation. The mitochondrial ultrastructure was assessed using transmission electronic microscopy. AS was associated with a dramatic drop in ABF and MAP combined with a severe hyperlactatemia 15 min after shock induction. CI-linked substrate state (197 ± 21 vs. 144 ± 21 pmol/s/mg, p < 0.05), OXPHOS activity by complexes I and II (411 ± 47 vs. 246 ± 33 pmol/s/mg, p < 0.05), and OXPHOS activity through complex II (316 ± 40 vs. 203 ± 28 pmol/s/mg, p < 0.05) were significantly impaired. ROS and RNS production was not significantly increased, but SODs activity was significantly higher in the AS group (11.15 ± 1.02 vs. 15.50 ± 1.40 U/mL/mg protein, p = 0.02). Finally, cardiac lipid peroxidation was significantly increased in the AS group (8.50 ± 0.67 vs. 12.17 ± 1.44 µM/mg protein, p < 0.05). No obvious changes were observed in the mitochondrial ultrastructure between CON and AS groups. Our experimental model of AS results in rapid and deleterious hemodynamic effects and was associated with a myocardial mitochondrial dysfunction with oxidative damage and without mitochondrial ultrastructural injury. Full article
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Systematic Review
Effect of Nitric Oxide Pathway Inhibition on the Evolution of Anaphylactic Shock in Animal Models: A Systematic Review
Biology 2022, 11(6), 919; https://doi.org/10.3390/biology11060919 - 16 Jun 2022
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Abstract
Nitric oxide (NO) induces vasodilation in various types of shock. The effect of pharmacological modulation of the NO pathway in anaphylactic shock (AS) remains poorly understood. Our objective was to assess, through a systematic review, whether inhibition of NO pathways (INOP) was beneficial [...] Read more.
Nitric oxide (NO) induces vasodilation in various types of shock. The effect of pharmacological modulation of the NO pathway in anaphylactic shock (AS) remains poorly understood. Our objective was to assess, through a systematic review, whether inhibition of NO pathways (INOP) was beneficial for the prevention and/or treatment of AS. A predesigned protocol for this systematic review was published in PROSPERO (CRD42019132273). A systematic literature search was conducted till March 2022 in the electronic databases PubMed, EMBASE, Scopus, Cochrane and Web of Science. Heterogeneity of the studies did not allow meta-analysis. Nine hundred ninety unique studies were identified. Of 135 studies screened in full text, 17 were included in the review. Among six inhibitors of NO pathways identified, four blocked NO synthase activity and two blocked guanylate cyclase downstream activity. Pre-treatment was used in nine studies and post-treatment in three studies. Five studies included both pre-treatment and post-treatment models. Overall, seven pre-treatment studies from fourteen showed improvement of survival and/or arterial blood pressure. Four post-treatment studies from eight showed positive outcomes. Overall, there was no strong evidence to conclude that isolated blockade of the NO/cGMP pathway is sufficient to prevent or restore anaphylactic hypotension. Further studies are needed to analyze the effect of drug combinations in the treatment of AS. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Article 1: Combined treatment with KV channel inhibitor 4-aminopyridine and either g-cystathionine lyase inhibitor ß-cyanoalanine or epinephrine restores blood pressure, increases serum vasoconstrictor levels, and improves survival in the Wistar rat model of anaphylactic shock
Authors: Abdelouahab Bellou, MD, PhD, MSc1,2, 3, 4*; Nacira Sennoun, PhD; Elhadi H. Aburawi MD, PhD3,§; Seth L. Alper, MD, PhD6; Ibrahim Abdallah Alfaki PhD7; Javed Yasin, PhD8 Subramanian Sekar, MPhar9,10; Mohamed Shafiuallah, MSc9; Suhail Alsalam, MD, PhD11; Abderrahim Nemmar, PhD9; Elsadig Kazzam, MD, PhD8; Paul Michel Mertes, MD, PhD, MS12; Suleiman Alhammadi, MD3,*

Article 2: Effect of protein Kinase C activation in hypotension and survival in a Wistar rat anaphylactic shock model
Authors: Fayez Alshamsi1, MD; Elhadi Aburawi2, MD, PhD (co-first author and co-corresponding author), Taoufik Zoubeidi3, PhD; Seth Alper4 MD, PhD; Javed Yasin1, PhD; Richardjayaraj Lawrencejayaraj2, PhD; Mohamed Shafiuallah5, MSc; Abderrahim Nemmar5, PhD;  Souhail AlSalam6, MD, PhD; Sekar Subramanian5,7, MPhar; Abdelouahab Bellou8,9,10 MD, PhD (co-first author and corresponding author)

Article 3: Impaired cardiac mitochondrial function in an experimental model of anaphylactic shock
Authors: Walid Oulehri 1,3, Olivier Collange 1,3, Charles Tacquard 1,3, Anne-Laure Charles 2,3, Bernard Geny 2,3, Paul Michel Mertes 1,3,*

Article 4: Role of the Nitric Oxide inhibition in the evolution of anaphylactic shock in animal models: A systematic Review
Authors: Maryam Alfalasi1; Sarah Alzaabi1 (co-first author);  Elhadi Aburawi2 (co-first author and co-corresponding author); Linda Östlundh3; Paul Michel Mertes4; Abdelouahab Bellou5,6,7,8 (co-first author, corresponding author). Article 5: Suhail Abdallah et al. Pathology and immunopathology of anaphylactic shock

Article 5: Role of anaphylactic shock mediators in anaphylactic shock
Authors: Paul Michel Mertes1,2 and Abdelouahab Bellou3,4,5

Article 6: Role of potassium channels in anaphylactic shock: A comprehensive narrative review
Authors: Abdelouahab Bellou1,2,3,*, Elhadi Aburawi4, Linda Östlundh5

Article 7: Pathology and Immunopathology of anaphylactic shock
Authors: Suhail Alsalam1,*, Ehadi Aburawi2, Abdelouahab Bellou3,4,5

Article 8: Genomic approach for the understanding of the pathophysiology of anaphylaxis
Author: Bernard Bihain

Article 9: A new inhibitor of potassium voltage dependent channels, the 3,4,5 aminopyridine improves the hypotension and survival in a Wistar rat anaphylactic shock model.
Authors: Richardjayaraj Lawrencejayaraj1; Elhadi H. Aburawi1; Taoufik Zoubeidi2; Javed Yasin3; Mohamed Shafiuallah4; Seth L. Alper5; Suhail Alsalam6; Paul Michel Mertes7,8; Abdelouahab Bellou9,10,11,*

Article 10: Analysis of the expression of the genes involved in the inflammation and the vasodilation induced in a Wistar rat model of anaphylactic shock
Authors: Abdelouahab Bellou1,2,3,*; Seth Alper4; Bernard Bihain5; Richardjayaraj Lawrencejayaraj6; Starling Emerald Bright David7; Elhadi Aburawi6

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