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Seminars in Immunopathology May 2018The epidermis closely interacts with nerve endings, and both epidermis and nerves produce substances for mutual sustenance. Neuropeptides, like substance P (SP) and... (Review)
Review
The epidermis closely interacts with nerve endings, and both epidermis and nerves produce substances for mutual sustenance. Neuropeptides, like substance P (SP) and calcitonin gene-related protein (CGRP), are produced by sensory nerves in the dermis; they induce mast cells to release vasoactive amines that facilitate infiltration of neutrophils and T cells. Some receptors are more important than others in the generation of itch. The Mas-related G protein-coupled receptors (Mrgpr) family as well as transient receptor potential ankyrin 1 (TRPA1) and protease activated receptor 2(Par2) have important roles in itch and inflammation. The activation of MrgprX1 degranulates mast cells to communicate with sensory nerve and cutaneous cells for developing neurogenic inflammation. Mrgprs and transient receptor potential vanilloid 4 (TRPV4) are crucial for the generation of skin diseases like rosacea, while SP, CGRP, somatostatin, β-endorphin, vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating polypeptide (PACAP) can modulate the immune system during psoriasis development. The increased level of SP, in atopic dermatitis, induces the release of interferon (IFN)-γ, interleukin (IL)-4, tumor necrosis factor (TNF)-α, and IL-10 from the peripheral blood mononuclear leukocytes. We are finally starting to understand the intricate connections between the skin neurons and resident skin cells and how their interaction can be key to controlling inflammation and from there the pathogenesis of diseases like atopic dermatitis, psoriasis, and rosacea.
Topics: Animals; Humans; Neurogenic Inflammation; Neuropeptides; Skin; Skin Diseases
PubMed: 29713744
DOI: 10.1007/s00281-018-0675-z -
Journal of Dermatological Science Jan 2019Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with...
BACKGROUND
Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.
OBJECTIVES
To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.
METHODS
Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.
RESULTS
Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.
CONCLUSIONS
These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.
Topics: Acetylcholine Release Inhibitors; Animals; Antimicrobial Cationic Peptides; Biopsy; Botulinum Toxins, Type A; Cell Degranulation; Cells, Cultured; Disease Models, Animal; Erythema; Humans; Injections, Intradermal; Mast Cells; Mice; Mice, Inbred C57BL; Primary Cell Culture; Rosacea; Skin; p-Methoxy-N-methylphenethylamine; Cathelicidins
PubMed: 30658871
DOI: 10.1016/j.jdermsci.2018.12.004 -
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 -
Cells May 2023Mast cells act as key effector cells of inflammatory responses through degranulation. Mast cell degranulation is induced by the activation of cell surface receptors,... (Review)
Review
Mast cells act as key effector cells of inflammatory responses through degranulation. Mast cell degranulation is induced by the activation of cell surface receptors, such as FcεRI, MRGPRX2/B2, and P2RX7. Each receptor, except FcεRI, varies in its expression pattern depending on the tissue, which contributes to their differing involvement in inflammatory responses depending on the site of occurrence. Focusing on the mechanism of allergic inflammatory responses by mast cells, this review will describe newly identified mast cell receptors in terms of their involvement in degranulation induction and patterns of tissue-specific expression. In addition, new drugs targeting mast cell degranulation for the treatment of allergy-related diseases will be introduced.
Topics: Humans; Mast Cells; Receptors, IgE; Hypersensitivity; Drug Development; Nerve Tissue Proteins; Receptors, Neuropeptide; Receptors, G-Protein-Coupled
PubMed: 37296626
DOI: 10.3390/cells12111506 -
Cells Apr 2023Mast cells (MCs) are the immune cells distributed throughout nearly all tissues, mainly in the skin, near blood vessels and lymph vessels, nerves, lungs, and the... (Review)
Review
Mast cells (MCs) are the immune cells distributed throughout nearly all tissues, mainly in the skin, near blood vessels and lymph vessels, nerves, lungs, and the intestines. Although MCs are essential to the healthy immune response, their overactivity and pathological states can lead to numerous health hazards. The side effect of mast cell activity is usually caused by degranulation. It can be triggered by immunological factors, such as immunoglobulins, lymphocytes, or antigen-antibody complexes, and non-immune factors, such as radiation and pathogens. An intensive reaction of mast cells can even lead to anaphylaxis, one of the most life-threatening allergic reactions. What is more, mast cells play a role in the tumor microenvironment by modulating various events of tumor biology, such as cell proliferation and survival, angiogenesis, invasiveness, and metastasis. The mechanisms of the mast cell actions are still poorly understood, making it difficult to develop therapies for their pathological condition. This review focuses on the possible therapies targeting mast cell degranulation, anaphylaxis, and MC-derived tumors.
Topics: Humans; Anaphylaxis; Mast Cells; Cell Degranulation; Skin
PubMed: 37190096
DOI: 10.3390/cells12081187 -
Journal of Advanced Pharmaceutical... 2022The discovery of new drugs has benefited significantly from the development of research in venomics, increasing our understanding of the envenomation processes. It has... (Review)
Review
The discovery of new drugs has benefited significantly from the development of research in venomics, increasing our understanding of the envenomation processes. It has been previously reported that honeybee venom (HBV) exhibits several pharmacological activities such as anti-inflammatory, antibacterial, antimutagenic, radioprotective, and anticancer activity and may inclusively act as a complementary treatment for SARS-CoV-2. It composition consists mainly on melittin, phospholipase A2, and apamin but other constituents such as hyaluronidase, mast cell degranulating peptide and secapin are also relevant for its bioactivity. However, and because HBV is not officially recognized as a drug, until now, the international community did not establish quality standards for it. To uncover its exact composition, and boost the discovery of HBV-derived drugs, a significant number of techniques were developed. In this review, a relevant overview of the so far published analytical methods for HBV characterization is organized with the aim to accelerate its future standardization. The literature search was performed within PubMed, Google Scholar, and Science Direct by selecting specific documents and exploring HBV evaluation.
PubMed: 35935688
DOI: 10.4103/japtr.japtr_166_21 -
Molecules (Basel, Switzerland) Dec 20232--Alkyl-l-ascorbic acids and 3--alkyl-l-ascorbic acids were synthesized, and their degranulation inhibitory activities were evaluated. Among ascorbic acid derivatives...
2--Alkyl-l-ascorbic acids and 3--alkyl-l-ascorbic acids were synthesized, and their degranulation inhibitory activities were evaluated. Among ascorbic acid derivatives with butyl, octyl, dodecyl, hexadecyl, and octadecyl groups introduced at the C-2 or C-3 positions, an AA derivative with a dodecyl group introduced at the C-3 position, 3--dodecyl-l-ascorbic acid (compound ), showed the strongest inhibitory activity against antigen-stimulated degranulation. Compound also inhibited calcium ionophore-stimulated degranulation. Compound , in which the hydroxyl group at the C-6 position of compound was substituted with an amino group, and compound , in which the dodecyloxy group at the C-3 position of compound was exchanged with a dodecylamino group, were synthesized, and these derivatives showed weaker inhibitory activity against antigen-stimulated degranulation than that of compound . In addition, orally administered compound inhibited passive cutaneous anaphylaxis reactions in mice with a potency equal to that of oxatomide, an antiallergic agent. These results suggest that compound may be a candidate for antiallergic treatment.
Topics: Animals; Mice; Anti-Allergic Agents; Ascorbic Acid
PubMed: 38202652
DOI: 10.3390/molecules29010069 -
Journal of Fungi (Basel, Switzerland) Jun 2021Humans have developed complex immune systems that defend against invading microbes, including fungal pathogens. Many highly specialized cells of the immune system share... (Review)
Review
Humans have developed complex immune systems that defend against invading microbes, including fungal pathogens. Many highly specialized cells of the immune system share the ability to store antimicrobial compounds in membrane bound organelles that can be immediately deployed to eradicate or inhibit growth of invading pathogens. These membrane-bound organelles consist of secretory vesicles or granules, which move to the surface of the cell, where they fuse with the plasma membrane to release their contents in the process of degranulation. Lymphocytes, macrophages, neutrophils, mast cells, eosinophils, and basophils all degranulate in fungal host defence. While anti-microbial secretory vesicles are shared among different immune cell types, information about each cell type has emerged independently leading to an uncoordinated and confusing classification of granules and incomplete description of the mechanism by which they are deployed. While there are important differences, there are many similarities in granule morphology, granule content, stimulus for degranulation, granule trafficking, and release of granules against fungal pathogens. In this review, we describe the similarities and differences in an attempt to translate knowledge from one immune cell to another that may facilitate further studies in the context of fungal host defence.
PubMed: 34208679
DOI: 10.3390/jof7060484