Development of different mast cell types in the opossum Didelphis albiventris

Anaphylaxis is a notorious type 2 immune response which may result in a systemic response and lead to death. A precondition for the unfolding of the anaphylactic shock is the secretion of inflammatory mediators from mast cells in response to an allergen, mostly through activation of the cells via the IgE-dependent pathway. While mast cells are specialized secretory cells that can secrete through a variety of exocytic modes, the most predominant mode exerted by the mast cell during anaphylaxis is compound exocytosis—a specialized form of regulated exocytosis where secretory granules fuse to one another. Here, we review the modes of regulated exocytosis in the mast cell and focus on compound exocytosis. We review historical landmarks in the research of compound exocytosis in mast cells and the methods available for investigating compound exocytosis. We also review the molecular mechanisms reported to underlie compound exocytosis in mast cells and expand further with reviewing key findings from other cell types. Finally, we discuss the possible reasons for the mast cell to utilize compound exocytosis during anaphylaxis, the conflicting evidence in different mast cell models, and the open questions in the field which remain to be answered.

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Platelet and Erythrocyte Extravasation across Inflamed Corneal Venules Depend on CD18, Neutrophils and Mast Cell Degranulation

International Journal of Molecular Sciences ◽

10.3390/ijms22147360 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7360

Author(s):

Angie De La Cruz ◽

Aubrey Hargrave ◽

Sri Magadi ◽

Justin A. Courson ◽

Paul T. Landry ◽

...

Keyword(s):

Mast Cell ◽

Cell Types ◽

Mast Cell Degranulation ◽

Wild Type ◽

Delayed Wound Healing ◽

Corneal Epithelial ◽

Corneal Abrasion ◽

Low Levels ◽

Endothelial Pores

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (KitW-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation.

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Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation

Journal of Experimental Medicine ◽

10.1084/jem.20150388 ◽

2015 ◽

Vol 212 (13) ◽

pp. 2289-2304 ◽

Cited By ~ 34

Author(s):

Binh L. Phong ◽

Lyndsay Avery ◽

Tina L. Sumpter ◽

Jacob V. Gorman ◽

Simon C. Watkins ◽

...

Keyword(s):

T Cells ◽

Mast Cell ◽

Signaling Pathways ◽

Cell Activation ◽

Molecular Mechanisms ◽

Late Phase ◽

Cell Types ◽

Mast Cell Activation ◽

Positive Role ◽

Ample Evidence

T cell (or transmembrane) immunoglobulin and mucin domain protein 3 (Tim-3) has attracted significant attention as a novel immune checkpoint receptor (ICR) on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance antiviral and antitumor immune responses. Tim-3 is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. At this point, little is known about the molecular mechanisms by which Tim-3 regulates the function of T cells or other cell types. We have focused on defining the effects of Tim-3 ligation on mast cell activation, as these cells constitutively express Tim-3 and are activated through an ITAM-containing receptor for IgE (FcεRI), using signaling pathways analogous to those in T cells. Using a variety of gain- and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcεRI ligation.

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Mast Cell-Specific Expression of Human Siglec-8 in Conditional Knock-in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20010019 ◽

2018 ◽

Vol 20 (1) ◽

pp. 19 ◽

Cited By ~ 13

Author(s):

Yadong Wei ◽

Krishan Chhiba ◽

Fengrui Zhang ◽

Xujun Ye ◽

Lihui Wang ◽

...

Keyword(s):

Flow Cytometry ◽

Mast Cell ◽

Mast Cells ◽

Es Cells ◽

Embryonic Stem ◽

Surface Protein ◽

Cell Types ◽

Mouse Strains ◽

Specific Expression

Sialic acid-binding Ig-like lectin 8 (Siglec-8) is expressed on the surface of human eosinophils, mast cells, and basophils—cells that participate in allergic and other diseases. Ligation of Siglec-8 by specific glycan ligands or antibodies triggers eosinophil death and inhibits mast cell degranulation; consequences that could be leveraged as treatment. However, Siglec-8 is not expressed in murine and most other species, thus limiting preclinical studies in vivo. Based on a ROSA26 knock-in vector, a construct was generated that contains the CAG promoter, a LoxP-floxed-Neo-STOP fragment, and full-length Siglec-8 cDNA. Through homologous recombination, this Siglec-8 construct was targeted into the mouse genome of C57BL/6 embryonic stem (ES) cells, and chimeric mice carrying the ROSA26-Siglec-8 gene were generated. After cross-breeding to mast cell-selective Cre-recombinase transgenic lines (CPA3-Cre, and Mcpt5-Cre), the expression of Siglec-8 in different cell types was determined by RT-PCR and flow cytometry. Peritoneal mast cells (dual FcεRI+ and c-Kit+) showed the strongest levels of surface Siglec-8 expression by multicolor flow cytometry compared to expression levels on tissue-derived mast cells. Siglec-8 was seen on a small percentage of peritoneal basophils, but not other leukocytes from CPA3-Siglec-8 mice. Siglec-8 mRNA and surface protein were also detected on bone marrow-derived mast cells. Transgenic expression of Siglec-8 in mice did not affect endogenous numbers of mast cells when quantified from multiple tissues. Thus, we generated two novel mouse strains, in which human Siglec-8 is selectively expressed on mast cells. These mice may enable the study of Siglec-8 biology in mast cells and its therapeutic targeting in vivo.

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Lack of histamine alters gastric mucosal morphology: comparison of histidine decarboxylase-deficient and mast cell-deficient mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00353.2003 ◽

2004 ◽

Vol 287 (5) ◽

pp. G1053-G1061 ◽

Cited By ~ 18

Author(s):

Eiji Nakamura ◽

Takashi Kataoka ◽

Kazuharu Furutani ◽

Keisuke Jimbo ◽

Takeshi Aihara ◽

...

Keyword(s):

Mast Cell ◽

Histidine Decarboxylase ◽

Serum Gastrin ◽

Cell Types ◽

Intragastric Ph ◽

Wild Type ◽

Mucosal Morphology ◽

Immunohistochemical Techniques ◽

Stomach Weight ◽

Deficient Mice

Histamine plays an important role in the regulation of gastric acid secretion; however, its role in maintenance of gastric morphology remains unclear. To clarify the necessity of histamine for gastric mucosal development and maintenance, we evaluated two different kinds of mice that lacked either mast cells (one of the gastric histamine-producing cell types) or histidine decarboxylase (HDC; a histamine-synthesizing enzyme). Measurements of stomach weight, intragastric pH, mucosal histamine levels, as well as serum gastrin and albumin levels were performed in mice. Gastric mucosal appearance was examined by immunohistochemical techniques. Although gastric mucosal histamine levels in mast cell-deficient mice were half of those observed in the wild-type mice, intragastric pH, serum gastrin levels, and gastric morphology at 12 mo were unchanged compared with the wild-type mice. In contrast, HDC-deficient mice possessed no detectable gastric histamine, but did exhibit hypergastrinemia, as well as marked increases in intragastric pH and stomach weight compared with the wild-type mice. Histological analysis revealed that 9-mo-old HDC-deficient mice demonstrated hyperplasia in the oxyntic glandular base region, as well as increased numbers of parietal and enterochromaffin-like cells. These results indicate that enterochromaffin-like cell-derived histamine is potentially involved in gastric mucosal morphology regulation.

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Immunomagnetic Isolation of Rat Bone Marrow-derived and Peritoneal Mast Cells

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215549704501215 ◽

1997 ◽

Vol 45 (12) ◽

pp. 1715-1722 ◽

Cited By ~ 13

Author(s):

Maria Celia Jamur ◽

Ana Cristina G. Grodzki ◽

Andrea N. Moreno ◽

William D. Swaim ◽

Reuben P. Siraganian ◽

...

Keyword(s):

Bone Marrow ◽

Mast Cell ◽

Mast Cells ◽

Cell Types ◽

Ultrastructural Level ◽

Immunomagnetic Separation ◽

Specific Cell ◽

Morphological Examination ◽

Immunomagnetic Isolation ◽

Rat Bone

Mast cells are difficult to purify from heterogeneous cell populations and to preserve, especially for pre-embedding immunostaining at the ultrastructural level. We have developed a technique that permits the isolation of a pure population of mast cells suitable for immunocytochemical studies. A rat mast cell-specific monoclonal antibody (MAb AA4) conjugated to tosylactivated Dynabeads 450 was used to immunomagnetically separate mast cells from rat bone marrow and peritoneal cell suspensions. Approximately 85% of the mast cells were recovered in the positive population that comprised virtually pure mast cells. After microwave fixation, morphological examination showed that the cells were intact and retained their ultrastructural detail. Mast cells in all stages of maturation were immunolabeled with a panel of antibodies after immunomagnetic separation. The combination of immunomagnetic separation followed by immunostaining should prove useful for the study of mast cell maturation and for the characterization of other specific cell types that are present in tissues in only limited numbers.

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Histochemical method for demonstrating quail mast cell types simultaneously

Biotechnic & Histochemistry ◽

10.1080/10520290902991394 ◽

2009 ◽

pp. 1-8

Author(s):

MK Harem ◽

N. Liman

Keyword(s):

Mast Cell ◽

Cell Types ◽

Histochemical Method

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Mouse connective tissue mast cell proteases tryptase and carboxypeptidase A3 play protective roles in itch induced by endothelin-1

Journal of Neuroinflammation ◽

10.1186/s12974-020-01795-4 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Elín I. Magnúsdóttir ◽

Mirjana Grujic ◽

Jessica Bergman ◽

Gunnar Pejler ◽

Malin C. Lagerström

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Connective Tissue ◽

Treatment Options ◽

Cell Types ◽

Tissue Type ◽

Human Mast Cell ◽

Knock Out ◽

Endothelin 1 ◽

Deficient Mice

Abstract Background Itch is an unpleasant sensation that can be debilitating, especially if it is chronic and of non-histaminergic origin, as treatment options are limited. Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor that also has the ability to induce a burning, non-histaminergic pruritus when exogenously administered, by activating the endothelin A receptor (ETAR) on primary afferents. ET-1 is released endogenously by several cell-types found in the skin, including macrophages and keratinocytes. Mast cells express ETARs and can thereby be degranulated by ET-1, and mast cell proteases chymase and carboxypeptidase A3 (CPA3) are known to either generate or degrade ET-1, respectively, suggesting a role for mast cell proteases in the regulation of ET-1-induced itch. The mouse mast cell proteases (mMCPs) mMCP4 (chymase), mMCP6 (tryptase), and CPA3 are found in connective tissue type mast cells and are the closest functional homologs to human mast cell proteases, but little is known about their role in endothelin-induced itch. Methods In this study, we evaluated the effects of mast cell protease deficiency on scratching behavior induced by ET-1. To investigate this, mMCP knock-out and transgenic mice were injected intradermally with ET-1 and their scratching behavior was recorded and analyzed. Results CPA3-deficient mice and mice lacking all three proteases demonstrated highly elevated levels of scratching behavior compared with wild-type controls. A modest increase in the number of scratching bouts was also seen in mMCP6-deficient mice, while mMCP4-deficiency did not have any effect. Conclusion Altogether, these findings identify a prominent role for the mast cell proteases, in particular CPA3, in the protection against itch induced by ET-1.

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