scholarly journals Future Needs in Mast Cell Biology

2019 ◽  
Vol 20 (18) ◽  
pp. 4397 ◽  
Author(s):  
Varricchi ◽  
de Paulis ◽  
Marone ◽  
Galli
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Biology ◽  
Human Myocardium ◽  
Atherosclerotic Plaques ◽  
Future Needs ◽  
Close Proximity ◽  
Health And Disease ◽  
Mouse Mast Cell ◽  
Paul Ehrlich

The pathophysiological roles of mast cells are still not fully understood, over 140 years since their description by Paul Ehrlich in 1878. Initial studies have attempted to identify distinct “subpopulations” of mast cells based on a relatively small number of biochemical characteristics. More recently, “subtypes” of mast cells have been described based on the analysis of transcriptomes of anatomically distinct mouse mast cell populations. Although mast cells can potently alter homeostasis, in certain circumstances, these cells can also contribute to the restoration of homeostasis. Both solid and hematologic tumors are associated with the accumulation of peritumoral and/or intratumoral mast cells, suggesting that these cells can help to promote and/or limit tumorigenesis. We suggest that at least two major subsets of mast cells, MC1 (meaning anti-tumorigenic) and MC2 (meaning pro-tumorigenic), and/or different mast cell mediators derived from otherwise similar cells, could play distinct or even opposite roles in tumorigenesis. Mast cells are also strategically located in the human myocardium, in atherosclerotic plaques, in close proximity to nerves and in the aortic valve. Recent studies have revealed evidence that cardiac mast cells can participate both in physiological and pathological processes in the heart. It seems likely that different subsets of mast cells, like those of cardiac macrophages, can exert distinct, even opposite, effects in different pathophysiological processes in the heart. In this chapter, we have commented on possible future needs of the ongoing efforts to identify the diverse functions of mast cells in health and disease.

scholarly journals The transcriptional program, functional heterogeneity, and clinical targeting of mast cells

2017 ◽  
Vol 214 (9) ◽  
pp. 2491-2506 ◽  
Author(s):  
Gökhan Cildir ◽  
Harshita Pant ◽  
Angel F. Lopez ◽  
Vinay Tergaonkar
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Inflammatory Diseases ◽  
Small Population ◽  
Transcriptional Program ◽  
Cell Functions ◽  
New Concepts ◽  
Health And Disease ◽  
Ige Mediated

Mast cells are unique tissue-resident immune cells that express an array of receptors that can be activated by several extracellular cues, including antigen–immunoglobulin E (IgE) complexes, bacteria, viruses, cytokines, hormones, peptides, and drugs. Mast cells constitute a small population in tissues, but their extraordinary ability to respond rapidly by releasing granule-stored and newly made mediators underpins their importance in health and disease. In this review, we document the biology of mast cells and introduce new concepts and opinions regarding their role in human diseases beyond IgE-mediated allergic responses and antiparasitic functions. We bring to light recent discoveries and developments in mast cell research, including regulation of mast cell functions, differentiation, survival, and novel mouse models. Finally, we highlight the current and future opportunities for therapeutic intervention of mast cell functions in inflammatory diseases.

scholarly journals Biochemical and immunological characterization of multiple glycoforms of mouse mast cell protease 1: comparison with an isolated murine serosal mast cell protease (MMCP-4)

1993 ◽  
Vol 294 (1) ◽  
pp. 127-135 ◽  
Author(s):  
G F J Newlands ◽  
D P Knox ◽  
S R Pirie-Shepherd ◽  
H R P Miller
Keyword(s):  
Mast Cell ◽  
Amino Acid ◽  
Mast Cells ◽  
Western Blotting ◽  
Trichinella Spiralis ◽  
Double Diffusion ◽  
Terminal Amino Acid ◽  
Mast Cell Protease ◽  
Terminal Amino ◽  
Mouse Mast Cell

Five highly soluble, chymotrypsin-like, neutral serine proteases, with molecular masses in the range 30-33 kDa, were isolated from Trichinella spiralis-infected mouse small intestine. These enzymes were closely related antigenically on Western blotting and by Ouchterlony double diffusion using a polyclonal, cross-absorbed, sheep antibody raised against mouse mast cell protease-1 (MMCP-1) and on the basis of N-terminal amino acid sequence analysis, were identified as variant forms of MMCP-1. Substrate and inhibitor analysis confirmed that the five variants (MMCP-1 A-E) had similar characteristics, although highly significant (P = 0.025 to P < 0.0001) variations in Km and kcat, were detected. Against human alpha 1-proteinase inhibitor the Ki for MMCP-1C (45 pM) was significantly (P < 0.0001) greater than those for the other proteases (0.76-2.2 pM). The differences in electrophoretic mobility are probably a result of variable glycosylation, since removal of N-linked carbohydrate produced a polypeptide of approx. 28 kDa in each case which was, like the native enzyme, immunoreactive on Western blotting. A much less soluble 28 kDa enzyme was isolated from serosal mast cells and identified as MMCP-4 by N-terminal amino acid sequencing. Like MMCP-1 it has chymotrypsin-like substrate specificities with activity at neutral pH. However, it was antigenically distinct from MMCP-1 and, using sheep anti-MMCP-1, was not detected on Western blotting or by Ouchterlony double diffusion, e.l.i.s.a. or immunohistochemistry. This last technique established that the MMCP-1 variants were uniquely present in enteric mast cells, thereby providing a highly selective means of distinguishing the mucosal and connective tissue mast cell subsets in the mouse.

scholarly journals Low c-kit expression of cultured mast cells of mi/mi genotype may be involved in their defective responses to fibroblasts that express the ligand for c-kit

Blood ◽  
1992 ◽  
Vol 80 (6) ◽  
pp. 1454-1462 ◽  
Author(s):  
Y Ebi ◽  
Y Kanakura ◽  
T Jippo-Kanemoto ◽  
T Tsujimura ◽  
T Furitsu ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tyrosine Phosphorylation ◽  
Messenger Rna ◽  
Tissue Type ◽  
Phenotypic Change ◽  
3T3 Fibroblasts ◽  
Mouse Mast Cell ◽  
And Function

Abstract Mutant mice of mi/mi genotype are osteopetrotic and deficient in tissue mast cells due to a defect in osteoclasts and mast cells. In an effort to further understand the mechanisms behind why mi/mi mouse-derived cultured mast cells (mi/mi-CMC) responded to interleukin-3 (IL-3), but not to the proliferative stimuli presented by fibroblasts, mi/mi-CMC and congenic normal (+/+) mouse-derived CMC (+/+-CMC), both of which expressed the phenotypic characteristics of immature mast cells, were cocultured with Swiss albino/3T3 fibroblasts in a medium containing IL- 3. In the in vitro CMC/fibroblast coculture, mi/mi-CMC did not acquire the phenotypes of connective tissue-type mast cells (CTMC), while +/+- CMC did. In addition, attachment of mi/mi-CMC to the fibroblasts was found to be significantly lower than that of +/+-CMC. Because the interaction of c-kit product with its ligand (stem cell factor [SCF]) is known to play an important role not only in proliferation and differentiation of mast cells but also in attachment of CMC to fibroblasts, the expression and function of c-kit were investigated in mi/mi-CMC and +/+-CMC. Recombinant rat SCF (rrSCF164) induced a dose- dependent proliferation of +/+-CMC. Also, rrSCF164 induced +/+-CMC to acquire the phenotypes of CTMC in the medium containing IL-3. By contrast, rrSCF164 did not stimulate the proliferation of mi/mi-CMC nor induce a phenotypic change of the cells from immature mast cells to mature, CTMC-like mast cells. Immunoblotting with antiphosphotyrosine antibody showed that rrSCF164 induced considerable tyrosine phosphorylation of 145- to 165-Kd protein, the product of c-kit, in +/+- CMC, whereas tyrosine phosphorylation of the protein was barely detectable in mi/mi-CMC. Northern blot and flow cytometry analyses showed that mi/mi-CMC expressed much less c-kit at both protein and message levels than +/+-CMC. Further, mi/mi-CMC were found to differ from +/+-CMC in the expression of mouse mast cell protease-6 (MMCP-6) and MMCP-2 messenger RNA transcripts. These results suggest that the gene product of the mi locus may be important in regulating the expression of gene products such as c-kit, and that mast cell deficiency of mi/mi mice appears to be due, at least in part, to impaired signaling through the c-kit receptor because of the low c-kit expression.

scholarly journals IgE Enhances Mouse Mast Cell FcεRI Expression In Vitro and In Vivo: Evidence for a Novel Amplification Mechanism in IgE-dependent Reactions

1997 ◽  
Vol 185 (4) ◽  
pp. 663-672 ◽  
Author(s):  
Masao Yamaguchi ◽  
Chris S. Lantz ◽  
Hans C. Oettgen ◽  
Ildy M. Katona ◽  
Tony Fleming ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Immunoglobulin E ◽  
Specific Antigen ◽  
Mast Cell Activation ◽  
Proinflammatory Mediators ◽  
Mouse Mast Cell

The binding of immunoglobulin E (IgE) to high affinity IgE receptors (FcεRI) expressed on the surface of mast cells primes these cells to secrete, upon subsequent exposure to specific antigen, a panel of proinflammatory mediators, which includes cytokines that can also have immunoregulatory activities. This IgE- and antigen-specific mast cell activation and mediator production is thought to be critical to the pathogenesis of allergic disorders, such as anaphylaxis and asthma, and also contributes to host defense against parasites. We now report that exposure to IgE results in a striking (up to 32-fold) upregulation of surface expression of FcεRI on mouse mast cells in vitro or in vivo. Moreover, baseline levels of FcεRI expression on peritoneal mast cells from genetically IgE-deficient (IgE −/−) mice are dramatically reduced (by ∼83%) compared with those on cells from the corresponding normal mice. In vitro studies indicate that the IgE-dependent upregulation of mouse mast cell FcεRI expression has two components: an early cycloheximide-insensitive phase, followed by a later and more sustained component that is highly sensitive to inhibition by cycloheximide. In turn, IgE-dependent upregulation of FcεRI expression significantly enhances the ability of mouse mast cells to release serotonin, interleukin-6 (IL-6), and IL-4 in response to challenge with IgE and specific antigen. The demonstration that IgE-dependent enhancement of mast cell FcεRI expression permits mast cells to respond to antigen challenge with increased production of proinflammatory and immunoregulatory mediators provides new insights into both the pathogenesis of allergic diseases and the regulation of protective host responses to parasites.

scholarly journals Fate of two mast cell tryptases in V3 mastocytosis and normal BALB/c mice undergoing passive systemic anaphylaxis: prolonged retention of exocytosed mMCP-6 in connective tissues, and rapid accumulation of enzymatically active mMCP-7 in the blood.

1996 ◽  
Vol 184 (3) ◽  
pp. 1061-1073 ◽  
Author(s):  
N Ghildyal ◽  
D S Friend ◽  
R L Stevens ◽  
K F Austen ◽  
C Huang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mast Cell ◽  
Mast Cells ◽  
Chromosome 17 ◽  
Macromolecular Complex ◽  
Connective Tissues ◽  
Systemic Anaphylaxis ◽  
Rich Domain ◽  
Passive Systemic Anaphylaxis ◽  
Mouse Mast Cell

The mouse mast cell protease granule tryptases designated mMCP-6 and mMCP-7 are encoded by highly homologous genes that reside on chromosome 17. Because these proteases are released when mast cells are activated, we sought a basis for distinctive functions by examining their fates in mice undergoing passive systemic anaphylaxis. 10 min-1 h after antigen (Ag) was administered to immunoglobulin (Ig)E-sensitized mice, numerous protease/proteoglycan macromolecular complexes appeared in the extracellular matrix adjacent to most tongue and heart mast cells of normal BALB/c mice and most spleen and liver mast cells of V3 mastocytosis mice. These complexes could be intensively stained by anti-mMCP-6 Ig but not by anti-mMCP-7 Ig. Shortly after Ag challenge of V3 mastocytosis mice, large amounts of properly folded, enzymatically active mMCP-7 were detected in the plasma. This plasma-localized tryptase was approximately 150 kD in its multimeric state and approximately 32 kD in its monomeric state, possessed an NH2 terminus identical to that of mature mMCP-7, and was not covalently bound to any protease inhibitor. Comparative protein modeling and electrostatic calculations disclosed that mMCP-6 contains a prominent Lys/Arg-rich domain on its surface, distant from the active site. The absence of this domain in mMCP-7 provides an explanation for its selective dissociation from the exocytosed macromolecular complex. The retention of exocytosed mMCP-6 in the extracellular matrix around activated tissue mast cells suggests a local action. In contrast, the rapid dissipation of mMCP-7 from granule cores and its inability to be inactivated by circulating protease inhibitors suggests that this tryptase cleaves proteins located at more distal sites.

scholarly journals Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4

2014 ◽  
Vol 62 ◽  
pp. 260-272 ◽  
Author(s):  
Sofie Nelissen ◽  
Tim Vangansewinkel ◽  
Nathalie Geurts ◽  
Lies Geboes ◽  
Evi Lemmens ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mast Cell ◽  
Mast Cells ◽  
Mast Cell Protease ◽  
Spinal Cord Damage ◽  
Post Traumatic ◽  
Mouse Mast Cell

scholarly journals Mast cell reaction to acupuncture on tongue

2019 ◽  
Vol 17 (3) ◽  
pp. 199-202
Author(s):  
N. Pirovski ◽  
Y. Staykova-Pirovska ◽  
D. Atanasova ◽  
N. Dimitrov
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Toluidine Blue ◽  
Sagittal Plane ◽  
Acupuncture Point ◽  
Visualization Method ◽  
Cell Reaction ◽  
Acupuncture Needle ◽  
Needle Tract ◽  
Close Proximity

PURPOSE: The aim is to find out the mast cells (MCs) reaction in tongue after experimental acupuncture. METHODS: For experiments were carried 10 adults rats (28 months age). The needles used for the acupuncture is 0.22x13mm, and were placed for 10 minutes into standard acupuncture point Ex-HN-10 (Juquan) corresponding to that of humans. This point is located on the upper surface in the sagittal plane of the tongue and is close to the center of the tongue body. As normal consequence of every acupuncture is the forming of a needle tract and also here in the tissues of the rats tongue we could demonstrate this. This was done with a visualization method for the needle tract that we developed for tongue. The proximity of the needle tract was examined for MCs. Two stains were used for proper visualization: Toluidine blue and Bismarck brown staining. RESULTS: In close proximity of the needle tract we observed degranulation of MCs that was massive and few destroyed MCs in the needle tract itself. At a considerable distance from the MCs some discharged granules from them was found. CONCLUSIONS: There is a MCs reaction on the acupuncture of tongue that includes a degranulation of the MCs that was massive in proximity of the acupuncture needle tract. Some of the effects ot acupuncture could be due to the demonstrated MCs degranulation.

scholarly journals Basophils preferentially express mouse mast cell protease 11 among the mast cell tryptase family in contrast to mast cells

2009 ◽  
Vol 86 (6) ◽  
pp. 1417-1425 ◽  
Author(s):  
Tsukasa Ugajin ◽  
Toshiyuki Kojima ◽  
Kaori Mukai ◽  
Kazushige Obata ◽  
Yohei Kawano ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Mast Cell Tryptase ◽  
Mast Cell Protease ◽  
Mouse Mast Cell

scholarly journals Lipid Rafts in Mast Cell Biology

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Adriana Maria Mariano Silveira e Souza ◽  
Vivian Marino Mazucato ◽  
Maria Célia Jamur ◽  
Constance Oliver
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Lipid Rafts ◽  
Cell Biology ◽  
Defense Mechanisms ◽  
Cell Structure ◽  
Critical Role ◽  
Allergic Diseases ◽  
Inflammatory Reactions ◽  
Pathological Conditions

Mast cells have long been recognized to have a direct and critical role in allergic and inflammatory reactions. In allergic diseases, these cells exert both local and systemic responses, including allergic rhinitis and anaphylaxis. Mast cell mediators are also related to many chronic inflammatory conditions. Besides the roles in pathological conditions, the biological functions of mast cells include roles in innate immunity, involvement in host defense mechanisms against parasites, immunomodulation of the immune system, tissue repair, and angiogenesis. Despite their growing significance in physiological and pathological conditions, much still remains to be learned about mast cell biology. This paper presents evidence that lipid rafts or raft components modulate many of the biological processes in mast cells, such as degranulation and endocytosis, play a role in mast cell development and recruitment, and contribute to the overall preservation of mast cell structure and organization.

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