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Frontiers in Immunology 2019Neutrophils are the most abundant innate immune cells. The pathogenic roles of neutrophils are related to chronic inflammation and autoimmune diseases. Psoriasis is a... (Review)
Review
Neutrophils are the most abundant innate immune cells. The pathogenic roles of neutrophils are related to chronic inflammation and autoimmune diseases. Psoriasis is a chronic systemic inflammatory disease affecting ~2-3% of the world population. The abundant presence of neutrophils in the psoriatic skin lesions serves as a typical histopathologic hallmark of psoriasis. Recent reports indicated that oxidative stress, granular components, and neutrophil extracellular traps from psoriatic neutrophils are related to the initial and maintenance phases of psoriasis. This review provides an overview on the recent (up to 2019) advances in understanding the role of neutrophils in the pathophysiology of psoriasis, including the effects of respiratory burst, degranulation, and neutrophil extracellular trap formation on psoriatic immunity and the clinical relationships.
Topics: Extracellular Traps; Humans; Immunity, Innate; Neutrophils; Psoriasis; Respiratory Burst
PubMed: 31649677
DOI: 10.3389/fimmu.2019.02376 -
Frontiers in Immunology 2021Asthma is a chronic and recurring airway disease, which related to mast cell activation. Many compounds derived from Chinese herbal medicine has promising effects on...
INTRODUCTION
Asthma is a chronic and recurring airway disease, which related to mast cell activation. Many compounds derived from Chinese herbal medicine has promising effects on stabilizing mast cells and decreasing inflammatory mediator production. Safranal, one of the active compounds from , shows many anti-inflammatory properties. In this study, we evaluated the effect of safranal in ovalbumin (OVA)-induced asthma model. Furthermore, we investigate the effectiveness of safranal on stabilizing mast cell and inhibiting the production of inflammatory mediators in passive systemic anaphylaxis (PSA) model.
METHODS
OVA-induced asthma and PSA model were used to evaluate the effect of safranal Lung tissues were collected for H&E, TB, IHC, and PAS staining. ELISA were used to determine level of IgE and chemokines (IL-4, IL-5, TNF-α, and IFN-γ). RNA sequencing was used to uncovers genes that safranal regulate. Bone marrow-derived mast cells (BMMCs) were used to investigate the inhibitory effect and mechanism of safranal. Cytokine production (IL-6, TNF-α, and LTC) and NF-κB and MAPKs signaling pathway were assessed.
RESULTS
Safranal reduced the level of serum IgE, the number of mast cells in lung tissue were decreased and Th1/Th2 cytokine levels were normalized in OVA-induced asthma model. Furthermore, safranal inhibited BMMCs degranulation and inhibited the production of LTC, IL-6, and TNF-α. Safranal inhibits NF-κB and MAPKs pathway protein phosphorylation and decreases NF-κB p65, AP-1 nuclear translocation. In the PSA model, safranal reduced the levels of histamine and LTC in serum.
CONCLUSIONS
Safranal alleviates OVA-induced asthma, inhibits mast cell activation and PSA reaction. The possible mechanism occurs through the inhibition of the MAPKs and NF-κB pathways.
Topics: Allergens; Animals; Anti-Inflammatory Agents; Asthma; Cell Degranulation; Cyclohexenes; Cytokines; Disease Models, Animal; Disease Susceptibility; Female; Immunoglobulin E; Inflammation Mediators; Mast Cells; Mice; NF-kappa B; Ovalbumin; Signal Transduction; Terpenes
PubMed: 34093515
DOI: 10.3389/fimmu.2021.585595 -
Cell Communication and Signaling : CCS Apr 2022Myocardial infarction (MI) is one of the most common cardiac emergencies with high morbidity and is a leading cause of death worldwide. Since MI could develop into a... (Review)
Review
Myocardial infarction (MI) is one of the most common cardiac emergencies with high morbidity and is a leading cause of death worldwide. Since MI could develop into a life-threatening emergency and could also seriously affect the life quality of patients, continuous efforts have been made to create an effective strategy to prevent the occurrence of MI and reduce MI-related mortality. Numerous studies have confirmed that neutrophils play important roles in inflammation and innate immunity, which provide the first line of defense against microorganisms by producing inflammatory cytokines and chemokines, releasing reactive oxygen species, and degranulating components of neutrophil cytoplasmic granules to kill pathogens. Recently, researchers reported that neutrophils are closely related to the severity and prognosis of patients with MI, and neutrophil to lymphocyte ratio in post-MI patients had predictive value for major adverse cardiac events. Neutrophils have been increasingly recognized to exert important functions in MI. Especially, granule proteins released by neutrophil degranulation after neutrophil activation have been suggested to involve in the process of MI. This article reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Video abstract Neutrophils played a crucial role throughout the process of MI, and neutrophil degranulation was the crucial step for the regulative function of neutrophils. Both neutrophils infiltrating and neutrophil degranulation take part in the injury and repair process immediately after the onset of MI. Since different granule subsets (e g. MPO, NE, NGAL, MMP-8, MMP-9, cathelicidin, arginase and azurocidin) released from neutrophil degranulation show different effects through diverse mechanisms in MI. In this review, we reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Myeloperoxidase (MPO); Neutrophil elastase (NE); Neutrophil gelatinase-associated lipocalin (NGAL); Matrix metalloproteinase 8 (MMP-8); Matrix metalloproteinase 9 (MMP-9).
Topics: Humans; Lipocalin-2; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Myocardial Infarction; Neutrophil Activation
PubMed: 35410418
DOI: 10.1186/s12964-022-00824-4 -
International Journal of Molecular... Jun 2021Eosinophils are specialized white blood cells, which are involved in the pathology of diverse allergic and nonallergic inflammatory diseases. Eosinophils are... (Review)
Review
Eosinophils are specialized white blood cells, which are involved in the pathology of diverse allergic and nonallergic inflammatory diseases. Eosinophils are traditionally known as cytotoxic effector cells but have been suggested to additionally play a role in immunomodulation and maintenance of homeostasis. The exact role of these granule-containing leukocytes in health and diseases is still a matter of debate. Degranulation is one of the key effector functions of eosinophils in response to diverse stimuli. The different degranulation patterns occurring in eosinophils (piecemeal degranulation, exocytosis and cytolysis) have been extensively studied in the last few years. However, the exact mechanism of the diverse degranulation types remains unknown and is still under investigation. In this review, we focus on recent findings and highlight the diversity of stimulation and methods used to evaluate eosinophil degranulation.
Topics: Cell Degranulation; Eosinophils; Extracellular Traps; Humans; Hypersensitivity
PubMed: 34209362
DOI: 10.3390/ijms22137091 -
Frontiers in Immunology 2022Mas-related G protein-coupled receptor-X2 (MRGPRX2) expressed on mast cells (MCs) contributes to hypersensitivity reactions to cationic US-Food and Drug Administration...
Mas-related G protein-coupled receptor-X2 (MRGPRX2) expressed on mast cells (MCs) contributes to hypersensitivity reactions to cationic US-Food and Drug Administration (FDA) approved drugs such as the neuromuscular blocking agent, rocuronium. In addition, activation of MRGPRX2 by the neuropeptide substance P (SP) and the pro-adrenomedullin peptide (PAMP-12) is associated with a variety of cutaneous conditions such as neurogenic inflammation, pain, atopic dermatitis, urticaria, and itch. Thus, small molecules aimed at blocking MRGPRX2 constitute potential options for modulating IgE-independent MC-mediated disorders. Two inverse MRGPRX2 agonists, named C9 and C9-6, have recently been identified, which inhibit basal G protein activation and agonist-induced calcium mobilization in transfected HEK293 cells. Substance P serves as a balanced agonist for MRGPRX2 whereby it activates both G protein-mediated degranulation and β-arrestin-mediated receptor internalization. The purpose of this study was to determine if C9 blocks MRGPRX2's G protein and β-arrestin-mediated signaling and to determine its specificity. We found that C9, but not its inactive analog C7, inhibited degranulation in RBL-2H3 cells stably expressing MRGPRX2 in response to SP, PAMP-12 and rocuronium with an IC value of ~300 nM. C9 also inhibited degranulation as measured by cell surface expression of CD63, CD107a and β-hexosaminidase release in LAD2 cells and human skin-derived MCs in response to SP but not the anaphylatoxin, C3a or FcϵRI-aggregation. Furthermore, C9 inhibited β-arrestin recruitment and MRGPRX2 internalization in response to SP and PAMP-12. We found that a G protein-coupling defective missense MRGPRX2 variant (V282M) displays constitutive activity for β-arrestin recruitment, and that this response was significantly inhibited by C9. Rocuronium, SP and PAMP-12 caused degranulation in mouse peritoneal MCs and these responses were abolished in the absence of MrgprB2 or cells treated with pertussis toxin but C9 had no effect. These findings suggest that C9 could provide an important framework for developing novel therapeutic approaches for the treatment of IgE-independent MC-mediated drug hypersensitivity and cutaneous disorders.
Topics: Mice; Animals; Humans; Receptors, Neuropeptide; Cell Degranulation; Adrenomedullin; Receptors, IgE; Substance P; Calcium; Rocuronium; Pertussis Toxin; HEK293 Cells; Nerve Tissue Proteins; Receptors, G-Protein-Coupled; Mast Cells; Neuropeptides; Drug Hypersensitivity; beta-N-Acetylhexosaminidases; beta-Arrestins; Anaphylatoxins; Immunoglobulin E
PubMed: 36275683
DOI: 10.3389/fimmu.2022.1033794 -
Allergology International : Official... Jul 2023Chronic spontaneous urticaria (CSU) is a common skin disease without an etiology in the vast majority of cases. The similarity of symptoms and pathology to... (Review)
Review
Chronic spontaneous urticaria (CSU) is a common skin disease without an etiology in the vast majority of cases. The similarity of symptoms and pathology to allergen-induced skin reactions supports that skin mast cell IgE receptor activation is also involved in CSU. Accumulating evidence also supports a role for blood basophils in disease expression. Blood basopenia is noted in active CSU disease with the recruitment of blood basophils to skin lesion sites. Blood basophils further display altered IgE receptor mediated degranulation patterns in two phenotypes that improve in remission. In active CSU subjects, changes in IgE receptor signaling molecule expression levels accompany the altered degranulation function in blood basophils. The success of therapies targeting IgE in CSU patients have also shown that altered blood basophil phenotypes and enumeration have potential use as a disease biomarker.
Topics: Humans; Basophils; Receptors, IgE; Chronic Disease; Urticaria; Chronic Urticaria
PubMed: 37221123
DOI: 10.1016/j.alit.2023.05.001 -
Journal of Innate Immunity 2021
Topics: Animals; Anti-Bacterial Agents; Antigens, Helminth; Antitubercular Agents; Asthma; Cell Degranulation; Host-Pathogen Interactions; Humans; Immunity, Innate; Mast Cells; Mycobacterium tuberculosis; Tuberculosis
PubMed: 33887720
DOI: 10.1159/000516180 -
Clinical Reviews in Allergy & Immunology Dec 2022Mast cells originate from the CD34/CD117 hematopoietic progenitors in the bone marrow, migrate into circulation, and ultimately mature and reside in peripheral tissues.... (Review)
Review
Mast cells originate from the CD34/CD117 hematopoietic progenitors in the bone marrow, migrate into circulation, and ultimately mature and reside in peripheral tissues. Microbiota/metabolites and certain immune cells (e.g., Treg cells) play a key role in maintaining immune tolerance. Cross-linking of allergen-specific IgE on mast cells activates the high-affinity membrane-bound receptor FcεRI, thereby initiating an intracellular signal cascade, leading to degranulation and release of pro-inflammatory mediators. The intracellular signal transduction is intricately regulated by various kinases, transcription factors, and cytokines. Importantly, multiple signal components in the FcεRI-mast cell-mediated allergic cascade can be targeted for therapeutic purposes. Pharmacological interventions that include therapeutic antibodies against IgE, FcεRI, and cytokines as well as inhibitors/activators of several key intracellular signaling molecues have been used to inhibit allergic reactions. Other factors that are not part of the signal pathway but can enhance an individual's susceptibility to allergen stimulation are referred to as cofactors. Herein, we provide a mechanistic overview of the FcεRI-mast cell-mediated allergic signaling. This will broaden our scope and visions on specific preventive and therapeutic strategies for the clinical management of mast cell-associated hypersensitivity reactions.
Topics: Humans; Mast Cells; Receptors, IgE; Immunoglobulin E; Hypersensitivity; Allergens; Cytokines
PubMed: 36251242
DOI: 10.1007/s12016-022-08955-9 -
Frontiers in Immunology 2021Many adverse reactions to therapeutic drugs appear to be allergic in nature, and are thought to be triggered by patient-specific Immunoglobulin E (IgE) antibodies that... (Review)
Review
Many adverse reactions to therapeutic drugs appear to be allergic in nature, and are thought to be triggered by patient-specific Immunoglobulin E (IgE) antibodies that recognize the drug molecules and form complexes with them that activate mast cells. However, in recent years another mechanism has been proposed, in which some drugs closely associated with allergic-type events can bypass the antibody-mediated pathway and trigger mast cell degranulation directly by activating a mast cell-specific receptor called Mas-related G protein-coupled receptor X2 (MRGPRX2). This would result in symptoms similar to IgE-mediated events, but would not require immune priming. This review will cover the frequency, severity, and dose-responsiveness of allergic-type events for several drugs shown to have MRGPRX2 agonist activity. Surprisingly, the analysis shows that mild-to-moderate events are far more common than currently appreciated. A comparison with plasma drug levels suggests that MRGPRX2 mediates many of these mild-to-moderate events. For some of these drugs, then, MRGPRX2 activation may be considered a regular and predictable feature after administration of high doses.
Topics: Anaphylaxis; Animals; Atracurium; Cell Degranulation; Drug Hypersensitivity; Humans; Immunoglobulin E; Mast Cells; Morphine; Nerve Tissue Proteins; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Rocuronium; Vancomycin
PubMed: 34421893
DOI: 10.3389/fimmu.2021.676354