In vivo exit of c-kit+/CD49dhi/β7+ mucosal mast cell precursors from the bone marrow following infection with the intestinal nematode Trichinella spiralis

Blood ◽  
2004 ◽  
Vol 103 (7) ◽  
pp. 2655-2660 ◽  
Author(s):  
Joanne L. Pennock ◽  
Richard K. Grencis
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Trichinella Spiralis ◽  
Mucosal Mast Cell ◽  
Hematopoietic Tissue ◽  
In Vivo Experiments ◽  
Intestinal Nematode

Abstract We have used the parasite helminth Trichinella spiralis to study the generation and differentiation of mast cell progenitors in the bone marrow of mice, as this infection triggers an intestinal mastocytosis which correlates with parasite expulsion. C-kit+ mast cell progenitors have previously been defined by methylcellulose colony-forming units and by limiting dilution assays in vitro. In vivo experiments have demonstrated the essential requirement by mast cells for specific integrin expression. We have defined 2 c-kit+ populations in the bone marrow, one of which coexpresses CD49d/β7 integrin, a marker essential for small intestine immigration. We have confirmed the phenotype of these cells by using antagonistic anti-c-kit antibody in vivo. Our data show that the loss of c-kit+/β7+ cells from the bone marrow correlates with their appearance in the blood and precedes detection of mature mast cells in the gut by 3 days. This exit correlates with an increase in soluble stem cell factor (SCF) in the serum, suggesting that the c-kit/SCF interaction may be chemotactic or haptotactic in nature. This study shows that during infection the bone marrow environment generates mast cells destined for the intestinal mucosa before their exit into the periphery, indicating a clear interplay between infection site and hematopoietic tissue. (Blood. 2004;103:2655-2660)

Thrombopoietin Regulates Proliferation and Maturation of Murine Mast Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1707-1707
Author(s):  
Giovanni Migliaccio ◽  
Barbara Ghinassi ◽  
Lucia Centurione ◽  
Maria Zingariello ◽  
Lucia Bianchi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Cell Differentiation ◽  
Growth Factor ◽  
Mast Cells ◽  
Wild Type ◽  
Connective Tissues ◽  
Immature Cells

Abstract Megakaryocytopoiesis is regulated by extrinsic (interaction of the growth factor thrombopoietin, TPO with its receptor Mpl) and intrinsic (interaction between the trascription factors GATA-1 and Fog-1) factors. The observation that mice impaired for GATA-1 expression (i.e. harbouring the GATA-1low mutation) are defective not only in megakaryocyte maturation but also in mast cell differentiation (Migliaccio et al. J Exp Med197:281, 2003), led us to investigate whether TPO might control mast cell differentiation as well. We first observed that mice genetically unable to responde to TPO (Mplnull mice) express in the connective tissues 5 times more mast cells than their normal littermates. Then, we analysed the effects on mast cell differentiation of in vivo treatment with TPO. Normal mice, and their GATA-1low littermates, were injected i.p. with TPO (100 μg/kg/day per 5 days, kindly provided by Kirin Brewery, Japan) and the number of immature (Toluidinepos) and mature (AlcianBlue/Saphraninepos) mast cells present in the connective tissues of the animals, as well as the frequency of GATA-1pos and TUNELpos mast cells, was evaluated 14 days after treatment. In wild-type animals, TPO reduced the presence of GATA-1 in mast cells (by immuno-histochemistry) and increased the number of immature cells (from 320±28 to 852±60) and of those undergoing apoptosis (from 16±1 to 600±43). In contrast, in GATA-1low animals, TPO-treatment induced the expression of GATA-1 in mast cells while decreased the number of immature cells (from 1100±72 to 427±29) as well as that of apoptotic cells (from 600±45 to 60±2). The role of TPO on mast cell differentiation were further confirmed by the analysis of the effects exerted by the growth factor on in vitro differentiation of bone marrow derived mast cells (BMMC). In these experiments, wild type bone marrow and spleen cells were cultured for 21 days with SCF and IL-3 with or without TPO and BMMC differentiation measured on the basis of the number of cells expressing the phenotype c-kithigh/CD34high and FcεRIpos. In cultures stimulated with SCF and IL-3, all the cells expressed the phenotype c-kithigh/CD34high and FcεRIpos. In contrast, in cultures supplemented also with SCF, IL-3 and TPO, only 25% of the cells were c-kithigh/CD34high and none of them was FcεRIpos. These results establish a role for TPO in the control of mast cell differentiation (possibly by modulating the GATA-1 content of the cells) and unveil further similarities between the mechanism(s) controlling megakaryocyte and mast cell differentiation.

Notch Signaling-Dependant Expulsion of Parasites through Mast Cell-Mediated Immunity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1473-1473
Author(s):  
Mamiko Sakata-Yanagimoto ◽  
Etsuko Yamaguchi-Nakagami ◽  
Toru Sakai ◽  
Keiki Kumano ◽  
Atsushi Kunisato ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Notch Signaling ◽  
Cell Generation ◽  
Pre Treatment ◽  
And Function ◽  
Tgf Β1

Abstract [Background] Notch signaling is known to be important in hematopoiesis, but very little information is available about its significance in mast cells. Here we provide direct evidence that notch signaling is critical for both development and function of mast cells in vitro and in vivo. [Methods] A Lin− fraction of mouse bone marrow cells was cultured on immobilized Delta1 in the presence of SCF and IL-3, and emerging Lin−FcεRI+c-Kit+ mast cells were characterized. Next, production of mouse mast cell protease-1 (mMCP-1), which is specific for nematode infection through locally expressed TGF-β1 in vivo, by bone marrow-derived mast cells (BMMC) was analyzed after the stimulation with Delta1 in the presence of TGF-β1. Finally, mice were infected with Strongyloides venezuelensis after pre-treatment with Delta1, and expulsion of the worms was examined. [Results] Lin−FcεRI+c-Kit+ mast cells developed remarkably earlier if stimulated with Delta1 (at one week, 15% vs. 3%). DAPT, a γ-secretase inhibitor, blocked the Delta1 effect, while it did not affect the regular time-course mast cell generation by SCF and IL-3. SB431542, a selective inhibitor of TGF-β1 signaling, also blocked early mast cell generation by Delta1. Delta1 augmented mMCP-1 expression and secretion from BMMC by 50 fold. Both DAPT and SB431542 showed a dose-dependent inhibition of Delta1 effect on mMCP-1 expression and secretion. Pre-treatment of the hosts with Delta1 promoted the expulsion of S. venezuelensis, (left/inoculated ratios of worms, 3% vs. 40%) while Delta1 had no effect in the mast cell-deficient W/Wv mice. [Discussion] Our observations reveal that notch signaling regulates both development and function of mast cells in vitro in conjunction with TGF-β1 signaling. In vivo, it is also likely that Delta1 facilitates the functional maturation of intestinal mast cells to eradicate parasites. More precise mechanism of Delta1 action on mast cells in vivo is under a study.

scholarly journals Phenotypic changes of bone marrow-derived mast cells after intraperitoneal transfer into W/Wv mice that are genetically deficient in mast cells.

1987 ◽  
Vol 165 (3) ◽  
pp. 615-627 ◽  
Author(s):  
K Otsu ◽  
T Nakano ◽  
Y Kanakura ◽  
H Asai ◽  
H R Katz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Adoptive Transfer ◽  
Gel Filtration ◽  
Chondroitinase Abc ◽  
Indirect Immunofluorescence Staining ◽  
Deficient Mice

The ability of mouse IL-3-dependent, bone marrow culture-derived mast cells (BMMC) to generate serosal mast cells (SMC) in vivo after adoptive transfer to mast cell-deficient mice has been defined by chemical and immunochemical criteria. BMMC differentiated and grown from WBB6F1-+/+ mouse progenitor cells in medium containing PWM/splenocyte-conditioned medium synthesized a approximately 350,000 Mr protease-resistant proteoglycan bearing approximately 55,000 Mr glycosaminoglycans, as defined by gel filtration of each. Approximately 85% of the glycosaminoglycans bound to the cell-associated BMMC proteoglycans were chondroitin sulfates based upon their susceptibility to chondroitinase ABC digestion; HPLC of the chondroitinase ABC-generated unsaturated disaccharides revealed these glycosaminoglycans to be chondroitin sulfate E. As determined by heparinase and nitrous acid degradations, approximately 10% of the glycosaminoglycans bound to BMMC proteoglycans were heparin. In contrast, mast cells recovered from the peritoneal cavity of congenitally mast cell-deficient WBB6F1-W/Wv mice 15 wk after intraperitoneal injection of BMMC synthesized approximately 650,000 Mr protease-resistant proteoglycans that contained approximately 80% heparin glycosaminoglycans of approximately 105,000 Mr. Thus, after adoptive transfer, the SMC of the previously mast cell-deficient mice were like those recovered from the normal WBB6F1-+/+ mice that were shown to synthesize approximately 600,000 Mr proteoglycans that contained approximately 80% heparin glycosaminoglycans of approximately 115,000 Mr. As assessed by indirect immunofluorescence staining and flow cytometry using the B1.1 rat mAb (an antibody that recognizes an epitope located on the neutral glycosphingolipid globopentaosylceramide), approximately 5% of BMMC bound the antibody detectably, whereas approximately 72% of the SMC that were harvested from mast cell-deficient mice 15 wk after adoptive transfer of BMMC were B1.1-positive; approximately 82% of SMC from WBB6F1-+/+ mice bound the antibody. These biochemical and immunochemical data are consistent with the results of previous adoptive transfer studies that characterized mast cells primarily on the basis of morphologic and histochemical criteria. Thus, IL-3-dependent BMMC developed in vitro, cells that resemble mucosal mast cells, can give rise in vivo to SMC that express phenotypic characteristics of connective tissue mast cells.

scholarly journals Role of mucosal mast cells in early vascular permeability changes of intestinal DTH reaction in the rat

1998 ◽  
Vol 274 (5) ◽  
pp. G832-G839 ◽  
Author(s):  
Aletta D. Kraneveld ◽  
Thea Muis ◽  
Andries S. Koster ◽  
Frans P. Nijkamp
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Vascular Leakage ◽  
Mast Cell Activation ◽  
Mucosal Mast Cell ◽  
Mucosal Mast Cells

Previously, it was shown that depletion and stabilization of the mucosal mast cell around the time of challenge were very effective in reducing delayed-type hypersensitivity (DTH) reactions in the small intestine of the rat. The role of mucosal mast cells in the early component of intestinal DTH reaction was further investigated in this study. In vivo small intestinal vascular leakage and serum levels of rat mast cell protease II (RMCP II) were determined within 1 h after intragastric challenge of rats that had been sensitized with dinitrobenzene 5 days before. A separate group of rats was used to study vasopermeability in isolated vascularly perfused small intestine after in vitro challenge. To investigate the effects of mast cell stabilization on the early events of the DTH reaction, doxantrazole was used. The influence of sensory nerves was studied by means of neonatal capsaicin-induced depletion of sensory neuropeptides. Within 1 h after challenge, a significant increase in vascular permeability was found in vivo as well as in vitro. This was associated with a DTH-specific increase in RMCP II in the serum, indicating mucosal mast cell activation. In addition, doxantrazole treatment and caspaicin pretreatment resulted in a significant inhibition of the DTH-induced vascular leakage and an increase in serum RMCP II. These findings are consistent with an important role for mucosal mast cells in early vascular leakage changes of intestinal DTH reactions. In addition, sensory nervous control of mucosal mast cell activation early after challenge is demonstrated.

scholarly journals Mouse bone marrow-derived mast cells (mBMMC) obtained in vitro from mice that are mast cell-deficient in vivo express the same panel of granule proteases as mBMMC and serosal mast cells from their normal littermates.

1994 ◽  
Vol 180 (1) ◽  
pp. 67-73 ◽  
Author(s):  
K K Eklund ◽  
N Ghildyal ◽  
K F Austen ◽  
D S Friend ◽  
V Schiller ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Steady State ◽  
Mast Cells ◽  
Induced Expression ◽  
Mast Cell Protease ◽  
Steady State Levels ◽  
Mouse Mast Cell

The ear, skin, and purified serosal mast cells of WBB6F1/J-(+/+) (WB-(+/+)) and WCB6F1/J-(+/+) (WC-(+/+)) mice contain high steady-state levels of the transcripts that encode mouse mast cell protease (mMCP) 2, mMCP-4, mMCP-5, mMCP-6, and mouse mast cell carboxypeptidase A (mMC-CPA). In contrast, no mast cell protease transcripts are present in abundance in the ear and skin of WBB6F1/J-W/Wv (W/Wv) and WCB6F1/J-Sl/Sld (Sl/Sld) mice which are mast cell-deficient in vivo due to defects in their c-kit and c-kit ligand genes, respectively. We now report that the immature bone marrow-derived mast cells (mBMMC) obtained in vitro with recombinant interleukin 3 (rIL-3) or WEHI-3 cell conditioned medium from WB-(+/+), WC-(+/+), W/Wv, and Sl/Sld mice all contain high steady-state levels of the mMCP-2, mMCP-4, mMCP-5, mMCP-6, and mMC-CPA transcripts. As assessed immunohistochemically, mMCP-2 protein and mMCP-5 protein are also present in the granules of mBMMC from WB-(+/+), WC-(+/+), and W/Wv mice. That Sl/Sld and W/Wv mBMMC contain high steady-state levels of five granule protease transcripts expressed by the mature serosal, ear, and skin mast cells of their normal +/+ littermates suggests that c-kit-mediated signal transduction is not essential for inducing transcription of these protease genes. Because rIL-4 inhibits the rIL-10-induced expression of mMCP-1 and mMCP-2 in BALB/cJ mBMMC, the ability of rIL-4 to influence protease mRNA levels in WC-(+/+) mBMMC and W/Wv mBMMC was investigated. Although rIL-10 induced expression of the mMCP-1 transcript in WC-(+/+) and W/Wv mBMMC, rIL-4 was not able to suppress the steady-state levels of the mMCP-1 transcript or any other protease transcript in these cultured mast cells. Thus, not only do BALB/cJ mBMMC express fewer granule proteases than mBMMC from mast cell-deficient strains and their normal littermates but the subsequent induction of late-expressed proteases in BALB/cJ mBMMC is more tightly regulated by IL-3 and IL-4.

In-vitro and in-vivo Evaluation of Anti-asthmatic Activity of Eugenia jambolana bark

2021 ◽  
pp. 3337-3342
Author(s):  
Bhong Prabha N. ◽  
Naikawade Nilofar. S. ◽  
Mali Pratibha. R. ◽  
Bindu Madhavi. S.
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Animal Models ◽  
Aqueous Extract ◽  
Guinea Pigs ◽  
Bark Extract ◽  
Eugenia Jambolana ◽  
In Vivo Animal Models

Objectives: The present study designed to evaluate the Antiasthmatic activity of aqueous extract of bark of Eugenia Jambolana (AEEJ) on in vitro and in vivo animal models. Materials and methods: Different in vitro and in vivo animal models was used to study the anti asthmatic activity as isolated goat tracheal chain preparation, Acetylcholine and Histamine induced bronconstriction in guinea pigs, effect of drug extract on histamine release from mast cell was checked by clonidine-induced mast cell degranulation, and milk-induced eosinophilia and leukocytosis. Results: In-vitro study on goat tracheal chain preparation revealed that aqueous extract of Eugenia jambolana (AEEJ)bark exerted antagonistic effect on the histamine induced contraction. (P<0.05) The guinea pigs when exposed to 0.2% histamine aerosol showed signs of progressive dyspnoea leading to convulsions. AEEJ significantly prolonged the latent period of convulsions (PCT) as compared to control following the exposure of histamine (0.2%) aerosol (P<0.01). The observation of present study indicates aqueous extract of Eugenia jambolana shows significant inhibition of milk induced eosinophilia and leukocytosis. Group of animals pretreated with aqueous Eugenia jambolana bark extract showed significant reduction in degranulation of mast cells when challenged with clonidine. The prevention of degranulation process by the aqueous Eugenia jambolana bark extract (P<0.01) indicates a possible stabilizing effect on the mast cells, indicating mast cell stabilizing activity. Conclusions: Thus, AEEJ showed antihistaminic, mast cell stabilizing and protective in guinea pigs against histamine induced PCD, reduced eosinophilia and leukocytosis and hence possesses potential role in the treatment of asthma.

scholarly journals Multiple bidirectional alterations of phenotype and changes in proliferative potential during the in vitro and in vivo passage of clonal mast cell populations derived from mouse peritoneal mast cells

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 877-885 ◽  
Author(s):  
Y Kanakura ◽  
H Thompson ◽  
T Nakano ◽  
T Yamamura ◽  
H Asai ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tissue Type ◽  
Cell Populations ◽  
Proliferative Potential ◽  
Heparin Binding ◽  
Peritoneal Mast Cells ◽  
Proliferative Ability

Mouse peritoneal mast cells (PMC) express a connective tissue-type mast cell (CTMC) phenotype, including reactivity with the heparin-binding fluorescent dye berberine sulfate and incorporation of [35S] sulfate predominantly into heparin proteoglycans. When PMC purified to greater than 99% purity were cultured in methylcellulose with IL-3 and IL-4, approximately 25% of the PMC formed colonies, all of which contained both berberine sulfate-positive and berberine sulfate-negative mast cells. When these mast cells were transferred to suspension culture, they generated populations that were 100% berberine sulfate-negative, a characteristic similar to that of mucosal mast cells (MMC), and that synthesized predominantly chondroitin sulfate [35S] proteoglycans. When “MMC-like” cultured mast cells derived from WBB6F1-+/+ PMC were injected into the peritoneal cavities of mast cell-deficient WBB6F1- W/Wv mice, the adoptively transferred mast cell population became 100% berberine sulfate-positive. In methylcellulose culture, these “second generation PMC” formed clonal colonies containing both berberine sulfate-positive and berberine sulfate-negative cells, but exhibited significantly less proliferative ability than did normal +/+ PMC. Thus, clonal mast cell populations initially derived from single PMC exhibited multiple and bidirectional alterations between CTMC-like and MMC-like phenotypes. However, this process was associated with a progressive diminution of the mast cells' proliferative ability.

Kartogenin enhances the therapeutic effect of bone marrow mesenchymal stem cells derived exosomes in cartilage repair

Nanomedicine ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. 273-288 ◽  
Author(s):  
Chun Liu ◽  
Yun Li ◽  
Zhijian Yang ◽  
Zhiyou Zhou ◽  
Zhihao Lou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Effect ◽  
Bone Marrow Mscs ◽  
In Vivo Experiments ◽  
Marrow Mesenchymal Stem Cells ◽  
Cartilage Diseases

The effectiveness of mesenchymal stem cells (MSC) in the treatment of cartilage diseases has been demonstrated to be attributed to the paracrine mechanisms, especially the mediation of exosomes. But the exosomes derived from unsynchronized MSCs may be nonhomogeneous and the therapeutic effect varies between samples. Aim: To produce homogeneous and more effective exosomes for the regeneration of cartilage. Materials & methods: In this study we produced specific exosomes from bone marrow MSCs (BMSC) through kartogenin (KGN) preconditioning and investigated their performance in either in vitro or in vivo experiments. Results & conclusion: The exosomes derived from KGN-preconditioned BMSCs (KGN-BMSC-Exos) performed more effectively than the exosomes derived from BMSCs (BMSC-Exos). KGN preconditioning endowed BMSC-Exos with stronger chondral matrix formation and less degradation.

scholarly journals Reevaluation of reserpine-induced suppression of contact sensitivity. Evidence that reserpine interferes with T lymphocyte function independently of an effect on mast cells.

1985 ◽  
Vol 162 (6) ◽  
pp. 1935-1953 ◽  
Author(s):  
Y A Mekori ◽  
G L Weitzman ◽  
S J Galli
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
Mast Cells ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Intradermal Injection ◽  
Host Cells ◽  
Lymphocyte Function

It has been suggested that reserpine blocks expression of delayed hypersensitivity (DH) by depleting tissue mast cells of serotonin (5-HT), thereby preventing a T cell-dependent release of mast cell 5-HT necessary to localize and to amplify the DH response. However, reserpine blocks expression of DH in mast cell-deficient mice. We therefore decided to reevaluate the mechanism by which reserpine abrogates expression of cellular immunity, and investigated whether the drug might interfere with T cell activity in vitro or in vivo. At concentrations as low as 4 microM, reserpine profoundly suppressed baseline or antigen-augmented levels of [3H]thymidine incorporation by immune lymph node cells obtained from mice sensitized to the contactant oxazolone [I-LNC(Ox)]. This effect was observed both with I-LNC derived from normal mice and with I-LNC derived from congenitally mast cell-deficient W/Wv mice, cell preparations that lacked detectable mast cells, histamine, and 5-HT. Furthermore, treatment of I-LNC with reserpine (20 microM) for 1 h in vitro virtually abolished the ability of these cells to transfer CS to naive mice. This was not a cytolytic effect, as the viability of the I-LNC treated with reserpine was not affected, and washing of the reserpine-treated I-LNC before transfer fully restored their ability to orchestrate a CS response. The action of the drug was not mediated by an effect on mast cells, since the experiment could be performed using mast cell-deficient W/Wv mice as both donors and recipients of I-LNC. In addition, the effect was specific for the treated cells: mice that received reserpine-treated I-LNC(Ox) intravenously together with untreated I-LNC(DNFB) did not develop CS to Ox but responded normally to DNFB; and local intradermal injection of reserpine-treated I-LNC(Ox) which failed to transfer reactivity to Ox, did not interfere with the development of CS to DNFB at the same site. Finally, cotransfer experiments indicated that the effect of reserpine on the transfer of CS was not due to activation of suppressor cells. Our findings strongly suggest that whatever effects reserpine might have on immunologically nonspecific host cells, the drug's effects on sensitized T cells are sufficient to explain its ability to block cell-mediated immune responses in vivo.

Tyrosine kinase-deficient Wvc-kit induces mast cell adhesion and chemotaxis

1998 ◽  
Vol 275 (5) ◽  
pp. C1291-C1299 ◽  
Author(s):  
Jaroslaw Dastych ◽  
Dennis Taub ◽  
Mary C. Hardison ◽  
Dean D. Metcalfe
Keyword(s):  
Mast Cell ◽  
Cell Adhesion ◽  
Mast Cells ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Mouse Bone Marrow ◽  
Intact Cells ◽  
Protein Kinase C Inhibitors

W/Wvmice are deficient in tissue mast cells, and mast cells cultured from these mice do not proliferate in response to the c-kit ligand, stem cell factor (SCF). In this paper, we report that mouse bone marrow cultured mast cells derived from W/Wvmice do adhere to fibronectin in the presence of SCF and exhibit chemotaxis to SCF, and we explore this model for the understanding of c-kit-mediated signaling pathways. Both in vitro and in vivo (in intact cells) phosphorylation experiments demonstrated a low residual level of W/Wvc-kit protein phosphorylation. SCF-induced responses in W/Wvmast cells were abolished by the tyrosine kinase inhibitor herbimycin A and by the phospatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin but were not affected by protein kinase C inhibitors. These observations are consistent with the conclusions that Wvc-kit initiates a signaling process that is PI 3-kinase dependent and that mutated Wvc-kit retains the ability to initiate mast cell adhesion and migration.

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