scholarly journals Role of mast cells in the generation of a T-helper type 2 dominated anti-helminthic immune response

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Nathan M. Ryan ◽  
Steve Oghumu
Keyword(s):  
Immune Response ◽  
Mast Cell ◽  
Mast Cells ◽  
Immune Cells ◽  
The Body ◽  
Peripheral Tissues ◽  
Adaptive Immune ◽  
Worm Expulsion ◽  
Deficient Mice

Abstract Mast cells are long-lived, innate immune cells of the myeloid lineage which are found in peripheral tissues located throughout the body, and positioned at the interface between the host and the environment. Mast cells are found in high concentrations during helminth infection. Using Kitw-sh mast cell deficient mice, a recently published study in Bioscience Reports by Gonzalez et al. (Biosci. Rep., 2018) focused on the role of mast cells in the immune response to infection by the helminth Hymenolepis diminuta. The authors showed that mast cells play a role in the modulation of Th2 immune response characterized by a unique IL-4, IL-5 and IL-13 cytokine profile, as well as subsequent robust worm expulsion during H. diminuta infection. Unlike WT mice which expelled H. diminuta at day 10, Kitw-sh deficient mice displayed delayed worm expulsion (day 14 post infection). Further, a possible role for mast cells in the basal expression of cytokines IL-25, IL-33 and thymic stromal lymphopoietin was described. Deletion of neutrophils in Kitw-sh deficient mice enhanced H. diminuta expulsion, which was accompanied by splenomegaly. However, interactions between mast cells and other innate and adaptive immune cells during helminth infections are yet to be fully clarified. We conclude that the elucidation of mechanisms underlying mast cell interactions with cells of the innate and adaptive immune system during infection by helminths can potentially uncover novel therapeutic applications against inflammatory, autoimmune and neoplastic diseases.

scholarly journals The emerging role of mast cell proteases in asthma

2019 ◽  
Vol 54 (4) ◽  
pp. 1900685 ◽  
Author(s):  
Gunnar Pejler
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Current Knowledge ◽  
Secretory Granules ◽  
Cross Linking ◽  
Lysosomal Hydrolases ◽  
Ige Receptor ◽  
Deficient Mice ◽  
Lines Of Evidence

It is now well established that mast cells (MCs) play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on MC-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which MCs influence asthma pathology. MCs contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of MC-restricted proteases. When MCs are activated, e.g. in response to IgE receptor cross-linking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The MC-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly, however, the role of the MC-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, the current knowledge of how the MC-restricted proteases impact on asthma is reviewed.

scholarly journals The role of the immune system in tendon healing: a systematic review

2020 ◽  
Vol 133 (1) ◽  
pp. 49-64 ◽  
Author(s):  
Emanuele Chisari ◽  
Laura Rehak ◽  
Wasim S Khan ◽  
Nicola Maffulli
Keyword(s):  
Systematic Review ◽  
Immune Response ◽  
Immune System ◽  
Mast Cells ◽  
Immune Cells ◽  
Tendon Healing ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Healing Response

Abstract Introduction The role of the immune system in tendon healing relies on polymorphonucleocytes, mast cells, macrophages and lymphocytes, the ‘immune cells’ and their cytokine production. This systematic review reports how the immune system affects tendon healing. Sources of data We registered our protocol (registration number: CRD42019141838). After searching PubMed, Embase and Cochrane Library databases, we included studies of any level of evidence published in peer-reviewed journals reporting clinical or preclinical results. The PRISMA guidelines were applied, and risk of bias and the methodological quality of the included studies were assessed. We excluded all the articles with high risk of bias and/or low quality after the assessment. We included 62 articles assessed as medium or high quality. Areas of agreement Macrophages are major actors in the promotion of proper wound healing as well as the resolution of inflammation in response to pathogenic challenge or tissue damage. The immune cells secrete cytokines involving both pro-inflammatory and anti-inflammatory factors which could affect both healing and macrophage polarization. Areas of controversy The role of lymphocytes, mast cells and polymorphonucleocytes is still inconclusive. Growing points The immune system is a major actor in the complex mechanism behind the healing response occurring in tendons after an injury. A dysregulation of the immune response can ultimately lead to a failed healing response. Areas timely for developing research Further studies are needed to shed light on therapeutic targets to improve tendon healing and in managing new way to balance immune response.

scholarly journals A Comparative Analysis of Mast Cell Quantification in Five Common Dermatoses: Lichen Simplex Chronicus, Psoriasis, Lichen Planus, Lupus, and Insect Bite/Allergic Contact Dermatitis/Nummular Dermatitis

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Nikhil Patel ◽  
Amir Mohammadi ◽  
Ronald Rhatigan
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Large Body ◽  
Dendritic Morphology ◽  
Hair Follicles ◽  
The Body ◽  
Tissue Sections ◽  
Lichen Simplex Chronicus ◽  
Allergic Contact

There is a large body of literature demonstrating an important role of mast cells in adaptive and innate immunity. The distribution of mast cells in the skin varies in different parts of the body. It is well known that mast cells are important for effector functions of classic IgE-associated allergic disorders as well as in host defense against infective agents and influence the manifestation of autoimmune diseases. We aimed to quantify mast cells in five common dermatoses and compare them statistically with respect to the immunostains. We retrieved paraffin-embedded tissue sections from the archives of the Pathology Department at the UF, Jacksonville, for five cases with each of the above diagnosis from the last three years. We performed CD-117 and tolidine blue stains on each one of them. The presence or absence of mast cells was evaluated and quantified. We observed that, in the skin, mast cells are mainly located close to the vessels, smooth muscle cells, hair follicles, and nerve ending. Our study showed that the mast cell distribution pattern is different across the two methods of staining for the five aforesaid dermatoses. The other important observation was the dendritic morphology of the mast cells.

scholarly journals Hypoxia/HIF Modulates Immune Responses

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 260
Author(s):  
Yuling Chen ◽  
Timo Gaber
Keyword(s):  
Immune Response ◽  
Cancer Progression ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Oxygen Availability ◽  
The Body ◽  
Low Oxygen ◽  
Adaptive Immune

Oxygen availability varies throughout the human body in health and disease. Under physiological conditions, oxygen availability drops from the lungs over the blood stream towards the different tissues into the cells and the mitochondrial cavities leading to physiological low oxygen conditions or physiological hypoxia in all organs including primary lymphoid organs. Moreover, immune cells travel throughout the body searching for damaged cells and foreign antigens facing a variety of oxygen levels. Consequently, physiological hypoxia impacts immune cell function finally controlling innate and adaptive immune response mainly by transcriptional regulation via hypoxia-inducible factors (HIFs). Under pathophysiological conditions such as found in inflammation, injury, infection, ischemia and cancer, severe hypoxia can alter immune cells leading to dysfunctional immune response finally leading to tissue damage, cancer progression and autoimmunity. Here we summarize the effects of physiological and pathophysiological hypoxia on innate and adaptive immune activity, we provide an overview on the control of immune response by cellular hypoxia-induced pathways with focus on the role of HIFs and discuss the opportunity to target hypoxia-sensitive pathways for the treatment of cancer and autoimmunity.

scholarly journals Anti-inflammatory and pro-resolving role of mast cells during resolution of local inflammation.

2021 ◽  
Author(s):  
◽  
Lisa Kornstädt
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
The Body ◽  
Type I ◽  
Local Inflammation ◽  
Ontology Term ◽  
Resolution Of Inflammation ◽  
Macrophage Phagocytosis ◽  
Anti Inflammatory

Mast cells are long-lived tissue-resident leukocytes, located most abundantly in the skin and mucosal surfaces. They belong to the first line of defence of the body, protecting against invading pathogens, toxins and allergens. Their secretory granules are densely packed with a plethora of mediators, which can be released immediately upon activation of the cell. Next to their role in IgE-mediated allergic diseases and in promoting inflammation, potential anti-inflammatory functions have been assigned to mast cells, depending on the biological setting. The aim of this thesis was to contribute to a better understanding of the role of mast cells during the resolution of a local inflammation. Therefore, in a first of step a suitable model of a local inflammation had to be identified. Since comparison of the two Toll-like receptor (TLR)-agonists zymosan and lipopolysaccharide (LPS), which are most commonly used to locally induce inflammation, revealed a systemic response after LPS-injection and a local inflammation after zymosan-injection, the TLR2 agonist zymosan was chosen for the subsequent experiments. Multi epitope ligand cartography (MELC) combined with statistical neighbourhood analysis showed that mast cells are located in an anti-inflammatory microenvironment next to M2 macrophages during resolution of inflammation, while neutrophils and M1 macrophages are located in the zymosan-filled core of the inflammation. Furthermore, infiltrating neutrophils during peak inflammation and an increasing population of macrophages phagocytosing neutrophils during resolution of inflammation could be observed. MELC as well as flow cytometry analysis of mast cell-deficient mice revealed a decreased phagocytosing activity of macrophages in the absence of mast cells. As an untargeted approach to identify mast cell-derived mediators induced by zymosan, mRNA sequencing of bone marrow-derived mast cells (BMMCs) was performed. Gene ontology term analysis of the sequencing data revealed the induction of the type I interferon (IFN) pathway as the dominant response. Contradicting previous studies, I could validate the production of IFN-β by mast cells in response to zymosan and LPS in vitro. Furthermore IFN-β expression by mast cells was also detected in vivo. In accordance with previous studies regarding other cell types the release of IFN-β by mast cells depends on endosomal signaling. The potential of IFN-β to enhance the phagocytosing activity of macrophages has been demonstrated recently. Besides IFN-β, various other mediators with reported enhancing effects on macrophage phagocytosis were also induced by zymosan in BMMCs, including Interleukin (IL)-1β, IL-4, IL-13, and Prostaglandin (PG) E2. Thus, either one of these mediators alone or a combination of them could promote macrophage phagocytosis. In conclusion, I herein present mast cells as a novel source for IFN-β induced by non-viral TLR ligands and demonstrate their enhancing effect on macrophage phagocytosis, thereby contributing to the resolution of inflammation.

scholarly journals Histamine and Antihistamines / Histamin i antihistamini

2015 ◽  
Vol 32 (1) ◽  
pp. 7-22
Author(s):  
Nikola Stojković ◽  
Snežana Cekić ◽  
Milica Ristov ◽  
Marko Ristić ◽  
Davor Đukić ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Allergic Diseases ◽  
The Body ◽  
Steady Increase ◽  
Cellular Events ◽  
Th1 And Th2 ◽  
Natural Component ◽  
Selection Of

Summary In recent years, there has been a steady increase in the prevalence of allergic diseases. Allergic immune response represents a complex network of cellular events involving numerous immune cells and mediators. It represents the interaction of innate and acquired immune response. The key role in the immune cascade is taken by histamine, a natural component of the body, which in the allergic inflammatory response is releasesd by the mast cells and basophils. The aim of this study was to highlight the role of histamine in allergic immunological events, their effect on Th1 and Th2 subpopulation of lymphocytes and the production of the corresponding cytokines, as well as the role of histamine blockers in the treatment of these conditions. Histamine achieves its effect by binding to the four types of its receptors, which are widely distributed in the body. Histamine blockers block a numerous effects of histamine by binding to these receptors. As a highly selective second-generation antihistamine, cetirizine not only achieves its effects by binding to H1 receptors, but also attenuates numerous events during the inflammatory process. Knowledge of the effects of histamine blockers, including cetirizine, may lead to the selection of proper therapy for the treatment of allegic diseases.

scholarly journals Mast Cell Deficiency Protects Mice from Surgery-Induced Neuroinflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Xiang Zhang ◽  
Hongquan Dong ◽  
Fei Wang ◽  
Jun Zhang
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Neuronal Apoptosis ◽  
Microglial Activation ◽  
Tibial Fracture ◽  
Wild Type ◽  
The Brain ◽  
Fracture Surgery ◽  
Deficient Mice

Neuroinflammation plays a key role in the occurrence and development of neurodegenerative diseases. Microglia, the resident immune cells in the brain, have been recognized to contribute to neuroinflammation. Previous studies have shown that activated mast cells may be involved in surgery-induced neuroinflammation and neuronal apoptosis by using pharmacological methods. This study is aimed at ascertaining the exactly role of mast cells on neuroinflammation with the mast cell-deficient mice. Adult male C57BL6/J wild-type (WT) and mast cell-deficient (C57BL6/J KitWsh/Wsh (Wsh)) mice underwent tibial fracture surgery. Blood-brain barrier (BBB) breakdown, microglial activation, and neuroinflammatory levels were examined at 1 day after surgery. Surgery-induced BBB breakdown, microglial activation, and neuroinflammatory levels were significantly, pharmacologically reduced using a mast cell stabilizer, cromolyn sodium in WT mice (P<0.05). These results were reproduced with mast cell deficiency. WT mice administered intraventricularly with cromolyn exhibited reduced BBB breakdown, microglial activation, and neuroinflammatory levels versus vehicle (P<0.05). But there was no effect of cromolyn versus vehicle in Wsh mice, clarifying the specificity of cromolyn on brain mast cells. These findings demonstrated that activated mast cells promote surgery-induced BBB breakdown and neuroinflammation in mice, and open up a new therapeutic target for neuroinflammation-related diseases.

scholarly journals The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells

2005 ◽  
Vol 202 (2) ◽  
pp. 217-224 ◽  
Author(s):  
Maiko Moriyama ◽  
Takahiro Sato ◽  
Hiromasa Inoue ◽  
Satoru Fukuyama ◽  
Hitoshi Teranishi ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Neutrophil Infiltration ◽  
Mast Cell Degranulation ◽  
Plasma Extravasation ◽  
Intraplantar Injection ◽  
Peripheral Tissues ◽  
Deficient Mice

Neuromedin U (NMU) is a neuropeptide that is expressed in the gastrointestinal tract and central nervous system. NMU interacts with two G protein–coupled receptors, NMU-R1 and NMU-R2. Whereas NMU-R2 localizes predominantly to nerve cells, NMU-R1 is expressed in peripheral tissues including lymphocytes and monocytes, suggesting a role of NMU in immunoregulation. However, the functions of NMU in peripheral tissues have not been clarified. In this study, using NMU-deficient mice, we first demonstrated that NMU plays an important role in mast cell-mediated inflammation. Complete Freund's adjuvant-induced mast cell degranulation as well as edema and neutrophil infiltration, which occurred weakly in mast cell–deficient WBB6F1-W/Wv mice, did not occur in NMU-deficient mice. Moreover, intraplantar injection of NMU into paws induced early inflammatory responses such as mast cell degranulation, vasodilation, and plasma extravasation in WT mice but not in WBB6F1-W/Wv mice. NMU-R1 was highly expressed in primary mast cells, and NMU induced Ca2+ mobilization and degranulation in peritoneal mast cells. These data indicate that NMU promotes mast cell–mediated inflammation; therefore, NMU receptor antagonists could be a novel target for pharmacological inhibition of mast cell–mediated inflammatory diseases.

scholarly journals Mast Cells Contribute to the Immunomodulatory Effect of the Biomaterial Microenvironment in a Gender Specific Manner

2020 ◽  
Author(s):  
Raymond M. Wang ◽  
Jessica Ungerleider ◽  
Yu Kawakami ◽  
Yuko Kawakami ◽  
Toshiaki Kawakami ◽  
...  
Keyword(s):  
Immune Response ◽  
Mast Cell ◽  
Mast Cells ◽  
Tissue Repair ◽  
M2 Macrophage ◽  
Male Response ◽  
Specific Manner ◽  
Biomaterial Scaffolds ◽  
Gender Specific ◽  
Deficient Mice

AbstractRegulation of the immune response contributes to the severity and outcomes in various disease conditions. Bioactive immunomodulatory biomaterials have shown promise for influencing these responses to promote tissue repair and regeneration. In this study, we investigated the role of mast cells in the regulation of the immune response to biomaterial scaffolds. In mast cell-deficient mice, there was dysregulation of the expected M1 to M2 macrophage transition typically induced by the biomaterial scaffold. Polarization progression deviated in a gender specific manner with an early transition to an M2 profile in female mice, while the male response was unable to properly transition past a pro-inflammatory M1 state. Both were reversed with mast cell adoptive transfer. Further investigation of the later stage immune response in male mice determined a sustained pro-inflammatory gene expression profile in deficient mice consisting of members from the IL-1 cytokine family and related downstream pathways. As mast cells were mainly associated with detrimental pro-inflammatory outcomes for biomaterial scaffolds, these results demonstrate their contribution to induced immunomodulatory therapies and support their potential as a critical immune regulatory element that can be manipulated for stimulating endogenous tissue repair.

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