Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID

Cells, Год журнала: 2023, Номер 12(5), С. 688 - 688

Опубликована: Фев. 22, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes disease 2019 (COVID-19). About 45% of COVID-19 patients experience several symptoms a few months after the initial infection and develop post-acute sequelae SARS-CoV-2 (PASC), referred to as “Long-COVID,” characterized by persistent physical mental fatigue. However, exact pathogenetic mechanisms affecting brain are still not well-understood. There is increasing evidence neurovascular inflammation in brain. precise role neuroinflammatory response that contributes severity long COVID pathogenesis clearly understood. Here, we review reports spike protein can cause blood–brain barrier (BBB) dysfunction damage neurons either directly, or via activation mast cells microglia release various molecules. Moreover, provide recent novel flavanol eriodictyol particularly suited for development an effective treatment alone together with oleuropein sulforaphane (ViralProtek®), all which have potent anti-viral anti-inflammatory actions.

Язык: Английский

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Topical drug delivery strategies for enhancing drug effectiveness by skin barriers, drug delivery systems and individualized dosing

Frontiers in Pharmacology, Год журнала: 2024, Номер 14

Опубликована: Янв. 16, 2024

Topical drug delivery is widely used in various diseases because of the advantages not passing through gastrointestinal tract, avoiding irritation and hepatic first-pass effect, reaching lesion directly to reduce unnecessary adverse reactions. The skin helps organism defend itself against a huge majority external aggressions one most important lines defense body. However, skin’s strong barrier ability also obstacle effectiveness topical medications. Allowing bioactive, composition pass stratum corneum as needed reach target site essential need for exert its therapeutic effect. state barrier, choice system composition, individualized disease detection dosing planning influence Nowadays, enhancing transdermal absorption topically applied drugs hottest research area. first improve all drugs. Excessive enhances accumulation at non-target sites occurrence This paper introduces strategies from three perspectives: delivery, describes current status shortcomings research, provides new directions ideas research.

Язык: Английский

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The Role of Crosstalk of Immune Cells in Pathogenesis of Chronic Spontaneous Urticaria

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Май 31, 2022

Chronic spontaneous urticaria (CSU) is defined as recurrent episodes of wheal development and/or angioedema for more than six weeks and at least twice a week. The core link in the pathogenesis CSU activation mast cells, T eosinophils, other immune cells infiltrating around small venules lesion. Increased vascular permeability, vasodilatation, recruitment inflammatory directly depend on cell mediators’ release. Complex regulatory systems tightly influence critical roles local microenvironment. bias toward Th2 inflammation autoantibodies derived from B histamine expressed by basophils, initiation extrinsic coagulation pathway eosinophils or monocytes exerts powerful modulatory influences cells. Cell-to-cell interactions between eosinophils/T also are regulators their function may involve CSU’s pathomechanism. This review summarizes up-to-date knowledge regarding crosstalk providing impetus to develop new research concepts treatment strategies CSU.

Язык: Английский

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Allergy, Anaphylaxis, and Nonallergic Hypersensitivity: IgE, Mast Cells, and Beyond

Medical Principles and Practice, Год журнала: 2022, Номер 31(6), С. 501 - 515

Опубликована: Янв. 1, 2022

IgE-mediated type I hypersensitivity reactions have many reported beneficial functions in immune defense against parasites, venoms, toxins, etc. However, they are best known for their role allergies, currently affecting almost one third of the population worldwide. allergic diseases result from a maladaptive 2 response that promotes synthesis IgE antibodies directed at special class antigens called allergens. bind to high-affinity receptors (FcεRI) on mast cells and basophils, sensitizing them get triggered subsequent encounter with cognate allergen. This release large variety inflammatory mediators including histamine responsible symptoms immediate hypersensitivity. The development 2-driven allergies is dependent complex interplay genetic environmental factors barrier surfaces host microbiome builds up during early life. While undoubtedly origin majority it has become clear similar responses can be by other types adaptive mediated via IgG or complement involving mediators. Likewise, various nonadaptive innate triggers expressed been found either directly launch reaction and/or amplify existing responses. review summarizes recent findings both IgE-dependent IgE-independent mechanisms hypersensitivities provides an update diagnosis allergy.

Язык: Английский

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Selected recent advances in understanding the role of human mast cells in health and disease

Journal of Allergy and Clinical Immunology, Год журнала: 2022, Номер 149(6), С. 1833 - 1844

Опубликована: Март 8, 2022

Язык: Английский

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Mast Cells at the Crossroads of Hypersensitivity Reactions and Neurogenic Inflammation

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 927 - 927

Опубликована: Янв. 23, 2025

Although mast cells have long been known, they are not yet fully understood. They traditionally recognized for their role in allergic reactions through the IgE/FcεRI axis, but different groups of surface receptors since characterized, which appear to be involved manifestation peculiar clinical features. In particular, MRGPRX2 has emerged as a crucial receptor degranulating human skin cells. Because cells’ close proximity peripheral nerve endings, it may play key neuroimmune interactions. This paper provides an overview cell contributions hypersensitivity and so-called “pseudoallergic” reactions, well update on neuroinflammatory implications main models airway diseases. cellular characteristics most relevant MC pathophysiology reappraised light recent advancements research. Molecular aspects related degranulation induced by IgE or analyzed compared, along with possible repercussions limitations future therapeutic perspectives.

Язык: Английский

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Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation

Annals of Allergy Asthma & Immunology, Год журнала: 2023, Номер 132(4), С. 440 - 454

Опубликована: Ноя. 10, 2023

Mast cells (MC) are ubiquitous in the body, and they critical for not only allergic diseases but also immunity inflammation, including having potential involvement pathophysiology of dysautonomias neuroinflammatory disorders. MC located perivascularly close to nerve endings sites such as carotid bodies, heart, hypothalamus, pineal gland, adrenal gland that would allow them regulate be affected by autonomic nervous system (ANS). stimulated allergens many other triggers some from ANS can affect release neurosensitizing, proinflammatory, vasoactive mediators. Hence, may able homeostatic functions seem dysfunctional conditions, postural orthostatic tachycardia syndrome, autism spectrum disorder, myalgic encephalomyelitis/chronic fatigue Long-COVID syndrome. The evidence indicates there is a possible association between these conditions associated with activation. There no effective treatment any form than minimizing symptoms. Given ways could activated numerous mediators released, it important develop inhibit stimulation ANS-relevant

Язык: Английский

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3D bio-printing-based vascular-microtissue electrochemical biosensor for fish parvalbumin detection

Food Chemistry, Год журнала: 2024, Номер 445, С. 138799 - 138799

Опубликована: Фев. 18, 2024

Язык: Английский

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Recombinant SARS-CoV-2 Spike Protein Stimulates Secretion of Chymase, Tryptase, and IL-1β from Human Mast Cells, Augmented by IL-33

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(11), С. 9487 - 9487

Опубликована: Май 30, 2023

SARS-CoV-2 infects cells via its spike (S) protein binding to surface receptor angiotensin-converting enzyme 2 (ACE2) and results in the production of multiple proinflammatory cytokines, especially lungs, leading what is known as COVID-19. However, cell source mechanism secretion such cytokines have not been adequately characterized. In this study, we used human cultured mast that are plentiful lungs showed recombinant full-length S (1-10 ng/mL), but receptor-binding domain (RBD), stimulates cytokine interleukin-1β (IL-1β) well proteolytic enzymes chymase tryptase. The IL-1β, chymase, tryptase augmented by co-administration interleukin-33 (IL-33) (30 ng/mL). This effect mediated toll-like 4 (TLR4) for IL-1β ACE2 These provide evidence contributes inflammation stimulating through different receptors could lead new targeted treatment approaches.

Язык: Английский

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Targeting Mast Cells in Allergic Disease: Current Therapies and Drug Repurposing

Cells, Год журнала: 2022, Номер 11(19), С. 3031 - 3031

Опубликована: Сен. 27, 2022

The incidence of allergic disease has grown tremendously in the past three generations. While current treatments are effective for some, there is considerable unmet need. Mast cells critical effectors inflammation. Their secreted mediators and receptors these have long been target allergy therapy. Recent drugs moved a step earlier mast cell activation, blocking IgE, IL-4, IL-13 interactions with their receptors. In this review, we summarize latest therapies targeting as well new clinical trials. addition, offer support repurposing FDA-approved to ways. With multitude highly selective available cancer, autoimmunity, metabolic disorders, drug offers optimism future

Язык: Английский

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