Wnt-3a Induces Cytokine Release in Human Mast Cells

Mast cells are well known for their detrimental effects in allergies and asthma, and Wnt signaling has recently been implicated in asthma and other airway diseases. However, it is not known if or how Wnts affect human mast cells. Since Wnt expression is elevated in individuals with asthma and is linked to a Th2 profile, we hypothesized that mast cells could be affected by Wnts in the context of asthma. We therefore sought to investigate the role of Wnt signaling in human mast cell development and activation. We first examined the expression of the 10 main Wnt receptors, Frizzled 1–10 (FZD1–10), and found expression of several FZDs in human mast cells. Treatment with purified recombinant Wnt-3a or Wnt-5a did not affect the proliferation or maturation of CD34+ progenitors into mast cells, as indicated by cellular expression of CD117 and FcεRI, activation by FcεRI crosslinking, and histamine and tryptase release. Furthermore, Wnt treatment did not change the phenotype from MCT to MCTC, since MrgX2 expression, compound 48/80-mediated activation, and carboxypeptidase A3 content were not affected. However, Wnt-3a activated WNT/β-catenin signaling in mature human mast cells, as revealed by stabilization of β-catenin, upregulation of IL-8 and CCL8 mRNA expression, and release of IL-8 protein. Thus, our data suggest that Wnt-3a activation of mast cells could contribute to the recruitment of immune cells in conditions associated with increased Wnt-3a expression, such as asthma.

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Comparison of the proteins of middle ear effusion with human mast cell proteins

The Journal of Laryngology & Otology ◽

10.1017/s0022215100132293 ◽

1995 ◽

Vol 109 (12) ◽

pp. 1146-1150

Author(s):

Yoseph Rakover ◽

Amir Shneyour ◽

Gabriel Rosen ◽

Yaacov Lensky

Keyword(s):

Mast Cells ◽

Middle Ear ◽

Human Mast Cell ◽

Middle Ear Effusion ◽

Secretory Otitis Media ◽

Human Mast Cells ◽

Gradient Gel Electrophoresis ◽

Protein Components ◽

Ear Effusion

AbstractIn order to clarify the role of mast cells in the aetiology of secretory otitis media (SOM), we compared the protein components of middle ear effusion (MEE) with human mast cells using acrylamide gradient gel electrophoresis and electrofocusing methods. This first direct comparison between the proteins of MEE and human mast cells has been made possible by a method developed in our laboratory for cultivation of human mast cells in tissue culture.On electrophoresis, we found that out of 12 bands of MEE proteins that were different from the serum, seven (58 per cent) had a similar electrophoretic migration rate (Rx) to mast cells. On electrofocusing, three of the four bands of MEE had a similar Rx to the mast cells. We have shown that proteins of mast cells and MEE had similar Rxs. Therefore, our study supports previous studies which suggests that mast cells play an important role in the aetiology of SOM.

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Selective Early Production of CCL20, or Macrophage Inflammatory Protein 3α, by Human Mast Cells in Response to Pseudomonas aeruginosa

Infection and Immunity ◽

10.1128/iai.71.1.365-373.2003 ◽

2003 ◽

Vol 71 (1) ◽

pp. 365-373 ◽

Cited By ~ 35

Author(s):

Tong-Jun Lin ◽

Lauren H. Maher ◽

Kaede Gomi ◽

Jeffrey D. McCurdy ◽

Rafael Garduno ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Mast Cells ◽

Immune Responses ◽

Immunoglobulin E ◽

Calcium Ionophore ◽

Human Mast Cell ◽

Gm Csf ◽

Human Mast Cells ◽

Inflammatory Protein ◽

Macrophage Inflammatory Protein

ABSTRACT Mast cells are important as sentinel cells in host defense against bacterial infection. Much of their effectiveness depends upon recruiting other immune cells; however, little is known about the mechanisms of this response. CCL20, also known as macrophage inflammatory protein-3α (MIP-3α), Exodus, and LARC, is a chemokine known to be a potent chemoattractant for immature dendritic cells and T cells. In this study, we examined the human mast cell production of both CCL20 and granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical cytokine for innate immune responses in the lung, in response to Pseudomonas aeruginosa. Reverse transcription-PCR and Western blot analysis demonstrated that the human mast cells (HMC-1) express CCL20 mRNA and are able to produce a significant amount (32.4 ng/ml) of CCL20 protein following stimulation by calcium ionophore and phorbol myristate acetate. Importantly, P. aeruginosa potently stimulated CCL20 production in human cord blood-derived mast cells (CBMC), with production peaking at 6 h after stimulation. This time course of expression was distinct from that of GM-CSF, which peaked after 24 to 48 h. Significant CCL20 production did not occur following immunoglobulin E-mediated activation of CBMC under conditions which induced a substantial GM-CSF response. Interestingly, the CCL20 response of mast cells to P. aeruginosa was relatively resistant to inhibition by the corticosteroid dexamethasone, interleukin-10, or cyclosporine, while GM-CSF production was potently inhibited. However, P. aeruginosa-induced CCL20 production was blocked by the protein kinase C (PKC) inhibitor Ro 31-8220 and a PKC pseudosubstrate. These results support a role for human mast cells in the initiation of immune responses to P. aeruginosa infection.

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Fine-tuning Mast Cells is Essential for the Maintenance and Regulation of the Systemic and Immune Homeostasis

Journal of Integrative Medicine ◽

10.30564/jim.v10i2.4111 ◽

2021 ◽

Vol 10 (2) ◽

pp. 60

Author(s):

Sylvia Frisancho-Kiss

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Scientific Literature ◽

Fine Tuning ◽

Viral Reservoir ◽

Evolutionary Perspective ◽

Cell Functions ◽

The Past ◽

Allergies And Asthma

During the past decades, populous expansion in mast cell scientific literature came forth with more, than forty-four thousand PubMed publications available to date. Such surge is due to the appreciation of the momentous role of mast cells in the evolution of species, in the development and maintenance of vital physiological functions, such as reproduction, homeostasis, and fluids, diverse immunological roles, and the potential of far-reaching effects despite minute numbers. While the emerging knowledge of the importance of mast cells in equilibrium comes of age when looking at the matter from an evolutionary perspective, the recognition of mast cells beyond detrimental performance in allergies and asthma, during protection against parasites, falters. Beyond well known classical functions, mast cells can process and present antigens,can serve as a viral reservoir, can respond to hormones and xenobiotics,initiate antiviral and antibacterial responses, phagocytosis, apoptosis, and participate in important developmental cornerstones. During evolution,upon the development of a sophisticated niche of innate and adaptive cell populations, certain mast cell functions became partially transmutable,yet the potency of mast cells remained considerable. Reviewing mast cells enables us to reflect on the certitude, that our sophisticated, complex physiology is rooted deeply in evolution, which we carry ancient remnants of, ones that may have decisive roles in our functioning. This communication sets out the goal of characterizing mast cells, particularly the aspects less in limelight yet of immense significance, without the aspiration exhaust it all.

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Expression of Functional TrkA Receptor Tyrosine Kinase in the HMC-1 Human Mast Cell Line and in Human Mast Cells

Blood ◽

10.1182/blood.v90.5.1807 ◽

1997 ◽

Vol 90 (5) ◽

pp. 1807-1820 ◽

Cited By ~ 105

Author(s):

See-Ying Tam ◽

Mindy Tsai ◽

Masao Yamaguchi ◽

Koji Yano ◽

Joseph H. Butterfield ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Tyrosine Kinase ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Human Mast Cell ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord ◽

Human Mast Cells

Abstract Nerve growth factor (NGF ) can influence mast cell development and function in murine rodents by interacting with its receptors on mast cells. We now report the identification of mRNA transcripts of full-length tyrosine kinase-containing trkA, trkB, and trkC neurotrophin receptor genes in HMC-1 human mast cell leukemia cells. Although HMC-1 cells lacked p75 mRNA, they expressed transcripts for the exon-lacking splice variant of trkA (trkAI), truncated trkB (trkB.T1), and truncated trkC. By flow cytometry, HMC-1 cells exhibited expression of TrkA, TrkB, and TrkC receptor proteins containing full-length tyrosine kinase domains. NGF stimulation of HMC-1 cells induced tyrosine phosphorylation of TrkA protein, increased expression of the early response genes c-fos and NGF1-A, and activation of ERK-mitogen–activated protein (MAP) kinase, results which indicate that TrkA receptors in HMC-1 cells are fully functional. Highly purified populations of human lung mast cells expressed mRNAs for trkA, trkB and trkC, whereas preparations of human umbilical cord blood-derived mast cells expressed mRNAs for trkA and trkC, but not trkB. Moreover, preparations of human umbilical cord blood-derived immature mast cells not only expressed mRNA transcript and protein for TrkA, but exhibited significantly higher numbers of chymase-positive cells after the addition of NGF to their culture medium for 3 weeks. In addition, HMC-1 cells expressed mRNAs for NGF, brain-derived neurotrophic factor (BDNF ), and neurotrophin-3 (NT-3), the cognate ligands for TrkA, TrkB, and TrkC, whereas NGF and BDNF transcripts were detectable in human umbilical cord blood mast cell preparations. Taken together, our findings show that human mast cells express a functional TrkA receptor tyrosine kinase and indicate that NGF may be able to promote certain aspects of mast cell development and/or maturation in humans. Our studies also raise the possibility that human mast cells may represent a potential source for neurotrophins.

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Mast Cells and Basophils in the Defense against Ectoparasites: Efficient Degradation of Parasite Anticoagulants by the Connective Tissue Mast Cell Chymases

International Journal of Molecular Sciences ◽

10.3390/ijms222312627 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12627

Author(s):

Zhirong Fu ◽

Srinivas Akula ◽

Anna-Karin Olsson ◽

Jukka Kervinen ◽

Lars Hellman

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Connective Tissue ◽

Blood Feeding ◽

Cathepsin G ◽

Human Mast Cell ◽

Mucosal Mast Cell ◽

Tissue Mast Cell ◽

Tick Feeding

Ticks, lice, flees, mosquitos, leeches and vampire bats need to prevent the host’s blood coagulation during their feeding process. This is primarily achieved by injecting potent anticoagulant proteins. Basophils frequently accumulate at the site of tick feeding. However, this occurs only after the second encounter with the parasite involving an adaptive immune response and IgE. To study the potential role of basophils and mast cells in the defense against ticks and other ectoparasites, we produced anticoagulant proteins from three blood-feeding animals; tick, mosquito, and leech. We tested these anticoagulant proteins for their sensitivity to inactivation by a panel of hematopoietic serine proteases. The majority of the connective tissue mast cell proteases tested, originating from humans, dogs, rats, hamsters, and opossums, efficiently cleaved these anticoagulant proteins. Interestingly, the mucosal mast cell proteases that contain closely similar cleavage specificity, had little effect on these anticoagulant proteins. Ticks have been shown to produce serpins, serine protease inhibitors, upon a blood meal that efficiently inhibit the human mast cell chymase and cathepsin G, indicating that ticks have developed a strategy to inactivate these proteases. We show here that one of these tick serpins (IRS-2) shows broad activity against the majority of the mast cell chymotryptic enzymes and the neutrophil proteases from human to opossum. However, it had no effect on the mast cell tryptases or the basophil specific protease mMCP-8. The production of anticoagulants, proteases and anti-proteases by the parasite and the host presents a fascinating example of an arms race between the blood-feeding animals and the mammalian immune system with an apparent and potent role of the connective tissue mast cell chymases in the host defense.

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Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells Both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

10.20944/preprints201910.0331.v1 ◽

2019 ◽

Author(s):

Tatsuki R. Kataoka ◽

Chiyuki Ueshima ◽

Masahiro Hirata ◽

Sachiko Minamiguchi ◽

Hironori Haga

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Cancer Metastasis ◽

Nk Cell ◽

Human Leukocyte ◽

Human Mast Cell ◽

Allergic Reactions ◽

Ige Receptor ◽

Human Mast Cells ◽

In Pregnancy

Killer immunoglobulin-like receptor (KIR) 2DL4 (CD158d) was previously thought to be a human NK-cell-specific protein but its expression has also been demonstrated in human mast cells. Mast cells are involved in allergic reactions via their KIT-mediated and IgE receptor-mediated responses. We recently detected the expression of KIR2DL4 in human cultured mast cells established from peripheral blood derived from healthy volunteers (PB-mast), a human mast cell line (LAD2), and non-neoplastic mast cells, including pathological specimens. An agonistic antibody against KIR2DL4 negatively regulates the KIT- and IgE-receptor-mediated responses of PB-mast and LAD2 cells. In addition, agonistic antibodies and human leukocyte antigen (HLA)-G, a natural ligand for KIR2DL4, induce the secretion from these cells of leukemia inhibitory factor and serine proteases, which have been implicated in pregnancy establishment and cancer metastasis. Therefore, KIR2DL4 stimulation with agonistic antibodies and recombinant HLA-G protein may enhance both processes, in addition to suppressing mast-cell-mediated allergic reactions.

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

British Medical Bulletin ◽

10.1093/bmb/ldz040 ◽

2020 ◽

Vol 133 (1) ◽

pp. 49-64 ◽

Cited By ~ 2

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.

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The Role of Natural Killer Cells and Mast Cells in Female Infertility and Associated Treatment Outcomes

Current Women s Health Reviews ◽

10.2174/1573404816666200206111550 ◽

2020 ◽

Vol 16 (2) ◽

pp. 102-106 ◽

Cited By ~ 1

Author(s):

Nahid Lorzadeh ◽

Nastaran Kazemirad

Keyword(s):

Mast Cells ◽

Natural Killer Cells ◽

Natural Killer ◽

Immune Cells ◽

Immunological Tolerance ◽

Immunosuppressive Drugs ◽

Immune Rejection ◽

Killer Cells ◽

Maternal Immune System

Introduction: One of the identified causes of infertility has been related to the inability to regulate immunological tolerance of the maternal immune system against the developing fetus, thereby inhibiting the process of implantation. Various immune cells have been identified to contribute to the concept of un-regulated immunological tolerance, such as mast cells (MCs) and natural killer cells (NK). There are available evidences that MC play a role in the pathogenesis of infertility diseases like endometriosis and NK in specific infertility disease. Objective: Presently, there are studies to formulate and develop immunosuppressive drugs in order to suppress or inhibit the process of immune rejection caused by maternal immune cells. In addition, there have been reports regarding the use of steroids for the treatment of miscarriage that can inhibit the activity of most immune cells. Conclusion: This review is to give a comprehensive mini-review on the role of immune cells, especially mast cells and NK cells in developing novel infertility treatment.

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Dengue Virus Selectively Induces Human Mast Cell Chemokine Production

Journal of Virology ◽

10.1128/jvi.76.16.8408-8419.2002 ◽

2002 ◽

Vol 76 (16) ◽

pp. 8408-8419 ◽

Cited By ~ 110

Author(s):

Christine A. King ◽

Robert Anderson ◽

Jean S. Marshall

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Virus Infection ◽

Dengue Virus ◽

Specific Antibody ◽

Human Mast Cell ◽

Dengue Virus Infection ◽

Human Mast Cells ◽

Virus Specific Antibody ◽

Rantes Production

ABSTRACT Severe dengue virus infections usually occur in individuals who have preexisting anti-dengue virus antibodies. Mast cells are known to play an important role in host defense against several pathogens, but their role in viral infection has not yet been elucidated. The effects of dengue virus infection on the production of chemokines by human mast cells were examined. Elevated levels of secreted RANTES, MIP-1α, and MIP-1β, but not IL-8 or ENA-78, were observed following infection of KU812 or HMC-1 human mast cell-basophil lines. In some cases a >200-fold increase in RANTES production was observed. Cord blood-derived cultured human mast cells treated with dengue virus in the presence of subneutralizing concentrations of dengue virus-specific antibody also demonstrated significantly (P < 0.05) increased RANTES production, under conditions which did not induce significant degranulation. Chemokine responses were not observed when mast cells were treated with UV-inactivated dengue virus in the presence or absence of human dengue virus-specific antibody. Neither antibody-enhanced dengue virus infection of the highly permissive U937 monocytic cell line nor adenovirus infection of mast cells induced a RANTES, MIP-1α, or MIP-1β response, demonstrating a selective mast cell response to dengue virus. These results suggest a role for mast cells in the initiation of chemokine-dependent host responses to dengue virus infection.

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