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Mast Cells in Human Health and Diseases 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 13786

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Dr. Giovanna Traina

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Guest Editor

Department of Pharmaceutical Sciences, University of Perugia, Via Romana, 06126 Perugia, Italy
Interests: inflammation; neuroinflammation; gut-brain axis; mast cells; learning and memory
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Increasing amounts of evidence suggest that mast cells play a crucial role in human health and diseases.

Mast cells are known to be cells involved in allergic reactions through degranulation and the release of a variety of mediators with vasoactive, inflammatory, and nociceptive activities. Mast cells are sensors of the environment, able to respond promptly and selectively. Mast cells are intriguing and multifactorial cells and play a leading role in various pathological conditions.

The localization of mast cells within the tissue and their expression of specific mediators, such as chymases or tryptases, are important pieces of evidence from the diagnostic point of view. Chronic inflammation is a common mediator of various disorders which include many pathological conditions, pain, migraine, depression, anxiety, autoimmune diseases, and fibromyalgia, but also Alzheimer’s disease, multiple sclerosis, atherosclerosis, and cardiovascular diseases. The modulation of the hyperactivity of mast cells and the reduction in the release of inflammatory factors could constitute new frontiers of therapeutic interventions aimed at preventing chronic inflammation.

Topics:

New developments in mast cell management in human disorders;
New molecular insights in mast cell control;
Mast cells and the microbiome;
Mast cells and nociception;
Mast cells and food allergies;
Mast cells and neuroinflammation;
Mast cells and stress.

Dr. Giovanna Traina
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

mast cells
human diseases
pain
cardiovascular diseases
microbiome
food allergy
stress
cancer

Published Papers (7 papers)

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Research

11 pages, 3326 KiB

Open AccessArticle

Factors Influencing Marker Expressions of Cultured Human Cord Blood-Derived Mast Cells

by Shahrzad Alimohammadi, Kana Masuda-Kuroki, Attila Gábor Szöllősi and Anna Di Nardo

Int. J. Mol. Sci. 2023, 24(19), 14891; https://doi.org/10.3390/ijms241914891 - 04 Oct 2023

Cited by 1 | Viewed by 908

Abstract

Mast cells (MCs) are tissue-resident immune cells of a hematopoietic origin that play vital roles in innate and adaptive immunity. Human MCs can be isolated and differentiated from various tissue sources, including cord blood, when supplemented with cytokines such as stem cell factor, interleukin 3, and interleukin 6. Our current research study has shown significant differences in the marker expressions of human cord blood-derived mast cells (hCBMCs) based on donor dependency and the type of medium used for culturing and differentiation. These findings are particularly relevant given the challenges of obtaining specialty media influencing MC phenotypic marker expressions. We found that hCBMCs cultured in StemSpanTM-XF medium had a moderate expression of mast/stem cell growth factor receptor Kit (c-KIT) (mRNA and protein), low expressions of FcεRI (mRNA) and TLR2 (mRNA and protein) but had high levels of MRGPRX2 (mRNA and protein) expressions. In contrast, hCBMCs cultured in Stem Line II medium expressed FcεRI and TLR2 (mRNA and protein) with higher c-KIT but had lower MRGPRX2 expressions compared to the hCBMCs cultured in the StemSpanTM-XF medium. These results suggest that it is crucial to consider both donor dependency and the medium when investigating MC functions and that further research is needed to fully understand the impact of these factors on the hCBMC marker expressions. Full article

(This article belongs to the Special Issue Mast Cells in Human Health and Diseases 2.0)

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8 pages, 1121 KiB

Open AccessCommunication

Increase in TPSB2 and TPSD1 Expression in Synovium of Hip Osteoarthritis Patients Who Are Overweight

by Maho Tsuchiya, Kensuke Fukushima, Ken Takata, Yoshihisa Ohashi, Katsufumi Uchiyama, Naonobu Takahira, Hiroki Saito, Ayumi Tsukada, Gen Inoue, Masashi Takaso and Kentaro Uchida

Int. J. Mol. Sci. 2023, 24(14), 11532; https://doi.org/10.3390/ijms241411532 - 16 Jul 2023

Cited by 1 | Viewed by 992

Abstract

While research suggests that increasing body mass index (BMI) is a risk factor for hip osteoarthritis (HOA), the mechanisms of this effect are not fully understood. Tryptases are among the main proteases found in mast cells (MCs) and contribute to OA pathology. TPSB2, which encodes β-tryptase, is increased in the synovium of overweight and obese knee OA patients. However, it remains unclear whether tryptase in the synovium of HOA is increased with increasing BMI. Here, we investigated tryptase genes (TPSB2 and TPSD1) in the synovium of overweight HOA patients. Forty-six patients radiographically diagnosed with HOA were allocated to two groups based on BMI, namely normal (<25 kg/m²) and overweight (25–29.99 kg/m²). TPSB2 and TPSD1 expression in the synovium of the two groups was compared using real-time polymerase chain reaction. To compare TPSB2 and TPSD1 expression in MCs between the groups, we isolated the MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF), extracted using magnetic isolation. TPSB2 and TPSD1 expression was increased in the overweight group compared with the normal group. Expression of both genes in the MC-RF was significantly higher than that in MC-PF in both groups. However, TPSB2 and TPSD1 expression levels in the MC-RF did not differ between the groups. Tryptase genes were highly expressed in the synovium of overweight HOA patients. Further investigation to reveal the role of tryptase in the relationship between increasing BMI and HOA pathology is required. Full article

(This article belongs to the Special Issue Mast Cells in Human Health and Diseases 2.0)

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20 pages, 6527 KiB

Open AccessArticle

Role of Mast-Cell-Derived RANKL in Ovariectomy-Induced Bone Loss in Mice

by Verena Fischer, Jasmin Maria Bülow, Benjamin Thilo Krüger, Deniz Ragipoglu, Anna Vikman, Melanie Haffner-Luntzer, Konstantinos Katsoulis-Dimitriou, Anne Dudeck and Anita Ignatius

Int. J. Mol. Sci. 2023, 24(11), 9135; https://doi.org/10.3390/ijms24119135 - 23 May 2023

Cited by 1 | Viewed by 1487

Abstract

Mast cells may contribute to osteoporosis development, because patients with age-related or post-menopausal osteoporosis exhibit more mast cells in the bone marrow, and mastocytosis patients frequently suffer from osteopenia. We previously showed that mast cells crucially regulated osteoclastogenesis and bone loss in ovariectomized, estrogen-depleted mice in a preclinical model for post-menopausal osteoporosis and found that granular mast cell mediators were responsible for these estrogen-dependent effects. However, the role of the key regulator of osteoclastogenesis, namely, receptor activator of NFκB ligand (RANKL), which is secreted by mast cells, in osteoporosis development has, to date, not been defined. Here, we investigated whether mast-cell-derived RANKL participates in ovariectomy (OVX)-induced bone loss by using female mice with a conditional Rankl deletion. We found that this deletion in mast cells did not influence physiological bone turnover and failed to protect against OVX-induced bone resorption in vivo, although we demonstrated that RANKL secretion was significantly reduced in estrogen-treated mast cell cultures. Furthermore, Rankl deletion in mast cells did not influence the immune phenotype in non-ovariectomized or ovariectomized mice. Therefore, other osteoclastogenic factors released by mast cells might be responsible for the onset of OVX-induced bone loss. Full article

(This article belongs to the Special Issue Mast Cells in Human Health and Diseases 2.0)

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14 pages, 2703 KiB

Open AccessArticle

Resveratrol Protects against Skin Inflammation through Inhibition of Mast Cell, Sphingosine Kinase-1, Stat3 and NF-κB p65 Signaling Activation in Mice

by Christopher D. Carlucci, Yvonne Hui, Alena P. Chumanevich, Piper A. Robida, John W. Fuseler, Mathew Sajish, Prakash Nagarkatti, Mitzi Nagarkatti and Carole A. Oskeritzian

Int. J. Mol. Sci. 2023, 24(7), 6707; https://doi.org/10.3390/ijms24076707 - 04 Apr 2023

Cited by 6 | Viewed by 2688

Abstract

Inflammation is pathogenic to skin diseases, including atopic dermatitis (AD) and eczema. Treatment for AD remains mostly symptomatic with newer but costly options, tainted with adverse side effects. There is an unmet need for safe therapeutic and preventative strategies for AD. Resveratrol (R) is a natural compound known for its anti-inflammatory properties. However, animal and human R studies have yielded contrasting results. Mast cells (MCs) are innate immune skin-resident cells that initiate the development of inflammation and progression to overt disease. R’s effects on MCs are also controversial. Using a human-like mouse model of AD development consisting of a single topical application of antigen ovalbumin (O) for 7 days, we previously established that the activation of MCs by a bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) initiated substantial skin remodeling compared to controls. Here, we show that daily R application normalized O-mediated epidermal thickening, ameliorated cell infiltration, and inhibited skin MC activation and chemokine expression. We unraveled R’s multiple mechanisms of action, including decreased activation of the S1P-producing enzyme, sphingosine kinase 1 (SphK1), and of transcription factors Signal Transducer and Activator of Transcription 3 (Stat3) and NF-κBp65, involved in chemokine production. Thus, R may be poised for protection against MC-driven pathogenic skin inflammation. Full article

(This article belongs to the Special Issue Mast Cells in Human Health and Diseases 2.0)

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19 pages, 2943 KiB

Open AccessArticle

Mast Cell Tryptase and Carboxypeptidase A3 in the Formation of Ovarian Endometrioid Cysts

by Dmitri Atiakshin, Olga Patsap, Andrey Kostin, Lyudmila Mikhalyova, Igor Buchwalow and Markus Tiemann

Int. J. Mol. Sci. 2023, 24(7), 6498; https://doi.org/10.3390/ijms24076498 - 30 Mar 2023

Cited by 2 | Viewed by 1262

Abstract

The mechanisms of ovarian endometrioid cyst formation, or cystic ovarian endometriosis, still remain to be elucidated. To address this issue, we analyzed the involvement of mast cell (MC) tryptase and carboxypeptidase A3 (CPA3) in the development of endometriomas. It was found that the formation of endometrioid cysts was accompanied by an increased MC population in the ovarian medulla, as well as by an MC appearance in the cortical substance. The formation of MC subpopulations was associated with endometrioma wall structures. An active, targeted secretion of tryptase and CPA3 to the epithelium of endometrioid cysts, immunocompetent cells, and the cells of the cytogenic ovarian stroma was detected. The identification of specific proteases in the cell nuclei of the ovarian local tissue microenvironment suggests new mechanisms for the regulatory effects of MCs. The cytoplasmic outgrowths of MCs propagate in the structures of the stroma over a considerable distance; they offer new potentials for MC effects on the structures of the ovarian-specific tissue microenvironment under pathological conditions. Our findings indicate the potential roles of MC tryptase and CPA3 in the development of ovarian endometriomas and infer new perspectives on their uses as pharmacological targets in personalized medicine. Full article

(This article belongs to the Special Issue Mast Cells in Human Health and Diseases 2.0)

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22 pages, 7711 KiB

Open AccessArticle

Degranulation of Murine Resident Cochlear Mast Cells: A Possible Factor Contributing to Cisplatin-Induced Ototoxicity and Neurotoxicity

by Betül Karayay, Heidi Olze and Agnieszka J. Szczepek

Int. J. Mol. Sci. 2023, 24(5), 4620; https://doi.org/10.3390/ijms24054620 - 27 Feb 2023

Cited by 1 | Viewed by 3107

Abstract

Permanent hearing loss is one of cisplatin’s adverse effects, affecting 30–60% of cancer patients treated with that drug. Our research group recently identified resident mast cells in rodents’ cochleae and observed that the number of mast cells changed upon adding cisplatin to cochlear explants. Here, we followed that observation and found that the murine cochlear mast cells degranulate in response to cisplatin and that the mast cell stabilizer cromoglicic acid (cromolyn) inhibits this process. Additionally, cromolyn significantly prevented cisplatin-induced loss of auditory hair cells and spiral ganglion neurons. Our study provides the first evidence for the possible mast cell participation in cisplatin-induced damage to the inner ear. Full article

(This article belongs to the Special Issue Mast Cells in Human Health and Diseases 2.0)

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13 pages, 2220 KiB

Open AccessArticle

The Crosstalk between Intestinal Epithelial Cells and Mast Cells Is Modulated by the Probiotic Supplementation in Co-Culture Models

by Raffaella di Vito, Alessia Di Mezza, Carmela Conte and Giovanna Traina

Int. J. Mol. Sci. 2023, 24(4), 4157; https://doi.org/10.3390/ijms24044157 - 19 Feb 2023

Cited by 1 | Viewed by 2504

Abstract

The intestinal epithelium constitutes a selectively permeable barrier between the internal and external environment that allows the absorption of nutrients, electrolytes, and water, as well as an effective defense against intraluminal bacteria, toxins, and potentially antigenic material. Experimental evidence suggest that intestinal inflammation is critically dependent on an imbalance of homeostasis between the gut microbiota and the mucosal immune system. In this context, mast cells play a crucial role. The intake of specific probiotic strains can prevent the development of gut inflammatory markers and activation of the immune system. Here, the effect of a probiotic formulation containing L. rhamnosus LR 32, B. lactis BL04, and B. longum BB 536 on intestinal epithelial cells and mast cells was investigated. To mimic the natural host compartmentalization, Transwell co-culture models were set up. Co-cultures of intestinal epithelial cells interfaced with the human mast cell line HMC-1.2 in the basolateral chamber were challenged with lipopolysaccharide (LPS), and then treated with probiotics. In the HT29/HMC-1.2 co-culture, the probiotic formulation was able to counteract the LPS-induced release of interleukin 6 from HMC-1.2, and was effective in preserving the epithelial barrier integrity in the HT29/Caco-2/ HMC-1.2 co-culture. The results suggest the potential therapeutic effect of the probiotic formulation. Full article

(This article belongs to the Special Issue Mast Cells in Human Health and Diseases 2.0)

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