Mediation of food protein-induced jejunal smooth muscle contraction in sensitized rats

1990 ◽  
Vol 259 (1) ◽  
pp. G6-G14 ◽  
Author(s):  
R. B. Scott ◽  
D. G. Gall ◽  
M. Maric
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Contractile Response ◽  
Specific Ige ◽  
Significant Loss ◽  
Tissue Type ◽  
Food Protein ◽  
Disodium Cromoglycate ◽  
Mast Cell Stabilizer

Alterations in myoelectric and motor activity are important features of food protein-induced intestinal anaphylaxis. To determine the mediator(s) involved, rats were sensitized by injection of egg albumin (10 micrograms ip), and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally oriented jejunal segments (mucosa intact) was examined in standard tissue baths in response to antigen (Ag) or other agents. Although control and sensitized tissues similarly contracted to stretch, bethanechol, histamine, or 5-hydroxytryptamine (5-HT), Ag contracted only sensitized segments. Contractile response 1) was specific to the sensitizing Ag, as bovine serum albumin did not induce contraction, and 2) could be passively transferred with serum containing specific IgE antibody. Mast cell degranulation after Ag challenge was suggested by a significant loss of granulated mast cells in sensitized compared with control rats challenged with Ag. Concanavalin A, which degranulates mucosal and connective tissue-type mast cells, and compound 48/80, which degranulates only connective tissue-type mast cells, produced a contractile response. Ag-induced contraction was significantly inhibited by the mucosal and connective tissue-type mast cell stabilizer doxantrazole (P less than 0.001) and the connective tissue mast cell stabilizer disodium cromoglycate (P less than 0.05). Diphenhydramine and cimetidine together blocked histamine-induced contraction but failed to affect Ag-induced contraction in sensitized tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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.

scholarly journals Mast cells degranulation affects angiogenesis in the rat uterine cervix during pregnancy

Reproduction ◽  
2004 ◽  
Vol 127 (3) ◽  
pp. 379-387 ◽  
Author(s):  
J Varayoud ◽  
J G Ramos ◽  
V L Bosquiazzo ◽  
M Muñoz-de-Toro ◽  
E H Luque
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Blood Vessels ◽  
Uterine Cervix ◽  
Vascular System ◽  
Mast Cell Degranulation ◽  
Endothelial Cell Proliferation ◽  
Disodium Cromoglycate ◽  
Mast Cell Stabilizer ◽  
Vascular Area

During pregnancy, it is essential that sufficient nutrients are supplied by the vascular system to support the dramatic modifications of the rat uterine cervix. Angiogenesis refers to the growth of new blood vessels from pre-existing microcirculation and mast cells have been associated with this process. This study examined the modifications of the vascular compartment and the distribution of mast cells on cervical tissue during pregnancy. Using disodium cromoglycate as a mast cell stabilizer, we determined the effects of the mast cell degranulation on cervical angiogenesis. Mast cell distribution and their degranulation status were evaluated by immunohistochemistry. Endothelial cell proliferation was measured by bromodeoxyuridine incorporation. Vascular areas (absolute and relative) and maturation indices were assessed by quantitative immunohistochemistry of von Willebrand factor and α-smooth muscle actin respectively. Mast cells were predominantly observed during the first half of pregnancy in the perivascular zones. The values of bromodeoxyuridine incorporation, absolute vascular area and vascular maturation index exhibited a significant increase throughout pregnancy. All animals that received mast cell stabilizer showed more than 40% of non-degranulated mast cells. Treated rats exhibited a decrease in endothelial proliferation and in relative vascular area; in addition, a large proportion of mature blood vessels was observed, suggesting a diminished level of new vessel formation. The effects of the mast cell stabilizer were sustained beyond the end of treatment. This is the first report that brings evidence that mast cell degranulation could be a necessary process to contribute to the normal angiogenesis of the rat cervix during pregnancy. Further investigations are needed to elucidate the possible implications of abnormal vascular development of the uterine cervix on the physiological process of ripening and parturition.

scholarly journals The rat c-kit ligand, stem cell factor, induces the development of connective tissue-type and mucosal mast cells in vivo. Analysis by anatomical distribution, histochemistry, and protease phenotype.

1991 ◽  
Vol 174 (1) ◽  
pp. 125-131 ◽  
Author(s):  
M Tsai ◽  
L S Shih ◽  
G F Newlands ◽  
T Takeishi ◽  
K E Langley ◽  
...  
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Stem Cell Factor ◽  
Tissue Type ◽  
Tyrosine Kinase Receptor ◽  
Kit Ligand ◽  
Mucosal Mast Cells

Mast cell development is a complex process that results in the appearance of phenotypically distinct populations of mast cells in different anatomical sites. Mice homozygous for mutations at the W or S1 locus exhibit several phenotypic abnormalities, including a virtual absence of mast cells in all organs and tissues. Recent work indicates that W encodes the c-kit tyrosine kinase receptor, whereas S1 encodes a c-kit ligand that we have designated stem cell factor (SCF). Recombinant or purified natural forms of the c-kit ligand induce proliferation of certain mast cell populations in vitro, and injection of recombinant SCF permits mast cells to develop in mast cell-deficient WCB6F1-S1/S1d mice. However, the effects of SCF on mast cell proliferation, maturation, and phenotype in normal mice in vivo were not investigated. We now report that local administration of SCF in vivo promotes the development of connective tissue-type mast cells (CTMC) in the skin of mice and that systemic administration of SCF induces the development of both CTMC and mucosal mast cells (MMC) in rats. Rats treated with SCF also develop significantly increased tissue levels of specific rat mast cell proteases (RMCP) characteristic of either CTMC (RMCP I) or MMC (RMCP II). These findings demonstrate that SCF can induce the expansion of both CTMC and MMC populations in vivo and show that SCF can regulate at least one cellular lineage that expresses c-kit, the mast cell, through complex effects on proliferation and maturation.

scholarly journals Localization of rat tryptase to a subset of the connective tissue type of mast cell.

1993 ◽  
Vol 41 (7) ◽  
pp. 961-969 ◽  
Author(s):  
Z Chen ◽  
A A Irani ◽  
T R Bradford ◽  
S S Craig ◽  
G Newlands ◽  
...  
Keyword(s):  
Mast Cell ◽  
Small Intestine ◽  
Mast Cells ◽  
Connective Tissue ◽  
Peritoneal Lavage ◽  
Tissue Type ◽  
Rat Skin ◽  
Double Labeling ◽  
Peritoneal Cells ◽  
Apparent Homogeneity

We examined the cellular distribution of rat tryptase in rat skin, lung, small intestine, and peritoneal lavage cells by immunohistochemical techniques. Tryptase purified to apparent homogeneity from rat skin was used to generate a goat polyclonal anti-rat tryptase antibody. Tryptase-containing cells were detected in lung, skin, and peritoneal lavage cells. Small intestine mucosa, on the other hand, showed few if any tryptase-positive cells. Sequential staining with Alcian blue and anti-tryptase antibody showed that tryptase is located only in mast cells. Sequential staining with safranin to identify the connective tissue type of mast cell and anti-tryptase antibody showed that tryptase resides only in this mast cell type. However, only a subpopulation of the safranin-stained mast cells contained tryptase. In lung, 53% of the mast cells stained with safranin; 94% contained tryptase. In skin, 80% stained with safranin; only 6% contained tryptase. In peritoneal cells, more than 95% of the mast cells were stained with safranin; 20% contained tryptase. In the bowel mucosa, where few cells are stained by safranin, no cells with tryptase were detected. The percentages of cells with chymase I that also contained tryptase were 80% and 84% for lung, 4% and 7% for skin, and 15% and 13% for peritoneal cells by respective simultaneous and sequential double labeling with anti-tryptase and anti-chymase I antibodies. This study suggests that the rat connective tissue type of mast cell is subdivided into two forms on the basis of the presence or absence of tryptase, whereas rat mucosal mast cells lack this enzyme. These results contrast with those in humans, in which tryptase is present in all mast cells, but are similar to mice, in which tryptase mRNA has been detected only in the connective tissue type.

scholarly journals Stimulation of mast cell chemotaxis by interleukin 3.

1989 ◽  
Vol 170 (4) ◽  
pp. 1421-1426 ◽  
Author(s):  
N Matsuura ◽  
B R Zetter
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Spleen Cell ◽  
Neutralizing Antibodies ◽  
Chemotactic Activity ◽  
Tissue Type ◽  
Hematopoietic Growth Factors ◽  
Gm Csf ◽  
Cell Chemotaxis

PWM-activated spleen cell-conditioned medium (SCCM) and a variety of purified hematopoietic growth factors were tested for their ability to stimulate chemotaxis of mouse connective tissue mast cells (CTMC). Of the agents tested, only IL-3 and SCCM promoted mast cell chemotaxis. Neither IL-2, IL-4, GM-CSF, nor endotoxin had any significant mast cell chemotactic activity. Neutralizing antibodies to mouse IL-3 blocked greater than 90% of the chemotactic activity of SCCM, suggesting that IL-3 is the predominant mast cell chemotactic factor produced by activated spleen cells. Our results demonstrate that mature connective tissue type mast cells are capable of moving toward a gradient of spleen cell-derived IL-3 and suggest that movement of mature mast cells toward lymphokines may influence the accumulation of mast cells at sites of inflammatory or immune reactions.

Distribution of mast cells in intestinal muscle of nematode-sensitized rats

1992 ◽  
Vol 262 (3) ◽  
pp. G477-G482 ◽  
Author(s):  
L. Marzio ◽  
P. Blennerhassett ◽  
D. Vermillion ◽  
S. Chiverton ◽  
S. Collins
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Longitudinal Muscle ◽  
Trichinella Spiralis ◽  
Maximum Response ◽  
Nippostrongylus Brasiliensis ◽  
Cell Numbers ◽  
Mast Cell Stabilizer ◽  
Functional Integrity

We examined the distribution and functional integrity of mast cells in intestinal longitudinal muscle in rats sensitized by two previous infections with Trichinella spiralis. A segment of jejunum was excluded from the gut before infection, and the remainder of the gut was anastomosed. Few mast cells were seen in muscle of noninfected control rats except in the region of the jejunal anastomosis. In rats sensitized by T. spiralis infection, mast cells were increased in number in the jejunum and the number of mast cells followed an aboral gradient down the entire length of the gut in continuity. In addition, mast cells were present in muscle of the excluded segment of sensitized rats. All mast cells were stained red with safranin. Functional integrity was assessed by the ability of mast cells to induce contraction after degranulation by antigen. In muscle from sensitized rats, contraction was induced in each region after exposure to T. spiralis antigen but not Nippostrongylus brasiliensis antigen. Contraction was inhibited by the mast cell stabilizer doxantrazole and the 5-hydroxytryptamine (5-HT) antagonist cyproheptadine. When antigen-induced contraction was expressed as a percentage of the maximum response of the tissue to exogenous 5-HT, the magnitude of contraction decreased along an aboral gradient down the intestine and correlated well (r2 = 0.878) with mast cell numbers. These results suggest that the increase in connective tissue mast cells in gut muscle after T. spiralis infection involves both local and systemic mechanisms.

Heparanase-mediated cleavage of macromolecular heparin accelerates release of granular components of mast cells from extracellular matrices

2014 ◽  
Vol 458 (2) ◽  
pp. 291-299 ◽  
Author(s):  
Nobuaki Higashi ◽  
Michihiko Waki ◽  
Mayumi Sue ◽  
Yusuke Kogane ◽  
Hiroaki Shida ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Cell Function ◽  
Secretory Granules ◽  
Extracellular Matrices ◽  
Regulatory Role ◽  
Tissue Type ◽  
Size Dependent

Connective tissue-type mast cells express heparin and heparanase in the secretory granules. Cleavage of granular heparin by heparanase accelerates release of granular components from collagen-based extracellular matrices. A size-dependent novel regulatory role of heparin for mast cell function is proposed.

The role of the mast cell in allergic bronchospasm

1987 ◽  
Vol 65 (3) ◽  
pp. 435-441 ◽  
Author(s):  
D. Befus
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Close Association ◽  
Late Phase ◽  
Cell Types ◽  
Specific Ige ◽  
Disodium Cromoglycate ◽  
Systematic Analysis ◽  
Surface Receptors

In allergic bronchospasm inhaled allergen interacts with specific IgE antibody on the surface of mast cells, inducing the release of mediators, particularly histamine and leukotrienes, which induce bronchoconstriction. Disodium cromoglycate, previously considered to be predominantly a mast cell stabilizing agent, is effective prophylactically in inhibition of early and late phase asthmatic reactions. However, the microenvironment of the airways contains many cell types and the precise role of mast cells is not clear. Lymphocytes, alveolar macrophages, eosinophils, platelets, and neutrophils possess low affinity surface receptors for IgE and can respond to allergen, releasing mediators that have diverse functions. These observations compound the problem of which mediator(s) is most important in pathogenesis of asthma. Moreover, mast cell products modulate the functions of many cells, and thus whether mast cells act directly or indirectly on bronchial smooth muscle requires clarification. Neuropeptides activate or modulate mast cells, and together with evidence of the close association of mast cells and nerves, these observations provide exciting new directions for investigation. Evidence that mast cells from different sites are heterogeneous in their response to stimuli and antiallergic drugs and differ in mediator production and function amplifies the problems identified above. In summary, the role of mast cells in bronchoconstriction is complex and systematic analysis of interactions between mast cells and other cells of the airways is essential.

scholarly journals Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 112 ◽  
Author(s):  
Keiko Yamada ◽  
Hitomi Sato ◽  
Kazuma Sakamaki ◽  
Mayumi Kamada ◽  
Yasushi Okuno ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
G Protein ◽  
Tissue Type ◽  
Cutaneous Inflammation ◽  
In Vivo Models ◽  
Expression Levels ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Steroidal anti-inflammatory drugs are widely used for the treatment of chronic cutaneous inflammation, such as atopic dermatitis, although it remains unknown how they modulate cutaneous mast cell functions. We investigated the effects of prolonged treatment with a synthetic glucocorticoid, dexamethasone, on murine connective tissue-type mast cells using in vitro and in vivo models. Our connective tissue-type bone marrow-derived cultured mast cell model was found to be sensitive to mast cell secretagogues, such as compound 48/80 and substance P, and higher expression levels of α subunit of a trimeric G protein, Gi1, and several Mas-related G protein-coupled receptor (Mrgpr) subtypes were observed in comparison with immature cultured mast cells. Secretagogue-induced degranulation and up-regulation of these genes was suppressed when cultured in the presence of dexamethasone. The profiles of granule constituents were drastically altered by dexamethasone. Topical application of dexamethasone down-modulated secretagogue-induced degranulation and the expression levels of several Mrgpr subtypes in cutaneous tissue. These results suggest that mast cell-mediated IgE-independent cutaneous inflammation could be suppressed by steroidal anti-inflammatory drugs through the down-regulation of G αi1 and several Mrgpr subtypes in mast cells.

scholarly journals Nerve growth factor induces development of connective tissue-type mast cells in vitro from murine bone marrow cells.

1991 ◽  
Vol 174 (1) ◽  
pp. 7-14 ◽  
Author(s):  
H Matsuda ◽  
Y Kannan ◽  
H Ushio ◽  
Y Kiso ◽  
T Kanemoto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Mast Cells ◽  
Connective Tissue ◽  
Bone Marrow Cells ◽  
Tissue Type ◽  
Phenotypic Change

The effect of nerve growth factor (NGF) on proliferation/differentiation of mast cells was investigated in vitro. Although NGF alone neither supported colony formation of bone marrow-derived cultured mast cells (BMCMC) nor induced development of mast cell colonies from nonadherent bone marrow cells (NBMC), addition of NGF to the suboptimal dose of interleukin 3 (IL-3) significantly increased the numbers of mast cell colonies produced by BMCMC or NBMC in methylcellulose. When stimulated by IL-3 alone, cells in mast cell colonies were not stained by berberine sulfate, a fluorescent dye. In contrast, mast cells developing in methylcellulose cultures obtaining both IL-3 and NGF were stained by berberine sulfate. The fluorescence was abolished by the treatment of heparinase but not of chondroitinase ABC, suggesting that mast cells stimulated by IL-3 and NGF produced and stored heparin proteoglycan. The histamine content of BMCMC maintained by IL-3 was also increased by addition of NGF. Since BMCMC showed mucosal mast cell-like phenotype, NGF appeared to induce the phenotypic change to connective tissue-type mast cells (CTMC). In the culture containing BMCMC, 3T3 fibroblasts, and IL-3, the phenotypic change of BMCMC to CTMC was observed as well. Since NGF was detected in this coculture and since addition of anti-NGF monoclonal antibody suppressed the phenotypic change, NGF produced by fibroblasts appeared to induce the phenotypic change. Neither BMCMC alone nor IL-3 alone increased the concentration of NGF. Therefore, there is a possibility that BMCMC stimulated by IL-3 may induce the production and/or release of NGF by fibroblasts.

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