Demonstration of human mast cell progenitors in the bone marrow

Salomonsson, Max; Ungerstedt, Johanna; Alvarado-Vázquez, Perla Abigail; Hallgren, Jenny

doi:10.1111/all.14004

Cited by 7 publications

(8 citation statements)

References 10 publications

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“…However, allergen sensitization and challenge induce accumulation of mast cells in the airways 7‐9 . The increase in lung mast cells in such models is dependent on the recruitment and maturation of mast cell progenitors (MCp) from blood to the lung, 10 and a similar MCp population is found in humans 11,12 . To understand what features of allergic asthma that are due to mast cells, mouse strains lacking mast cells due to loss of kit were used, and demonstrated conflicting results 7,13‐15 .…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9] The increase in lung mast cells in such models is dependent on the recruitment and maturation of mast cell progenitors (MCp) from blood to the lung, 10 and a similar MCp population is found in humans. 11,12 To understand what features of allergic asthma that are due to mast cells, mouse strains lacking mast cells due to loss of kit were used, and demonstrated conflicting results. 7,[13][14][15] Moreover, the observed phenotypes were often not due to loss of mast cells.…”

Section: Introductionmentioning

confidence: 99%

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Mast cell‐derived serotonin enhances methacholine‐induced airway hyperresponsiveness in house dust mite‐induced experimental asthma

Méndez-Enríquez

Alvarado-Vázquez

Abma

et al. 2021

Allergy

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Background Airway hyperresponsiveness (AHR) is a feature of asthma in which airways are hyperreactive to stimuli causing extensive airway narrowing. Methacholine provocations assess AHR in asthma patients mainly by direct stimulation of smooth muscle cells. Using in vivo mouse models, mast cells have been implicated in AHR, but the mechanism behind has remained unknown. Methods Cpa3Cre/+mice, which lack mast cells, were used to assess the role of mast cells in house dust mite (HDM)‐induced experimental asthma. Effects of methacholine in presence or absence of ketanserin were assessed on lung function and in lung mast cells in vitro. Airway inflammation, mast cell accumulation and activation, smooth muscle proliferation, and HDM‐induced bronchoconstriction were evaluated. Results Repeated intranasal HDM sensitization induced allergic airway inflammation associated with accumulation and activation of lung mast cells. Lack of mast cells, absence of activating Fc‐receptors, or antagonizing serotonin (5‐HT)2A receptors abolished HDM‐induced trachea contractions. HDM‐sensitized mice lacking mast cells had diminished lung‐associated 5‐HT levels, reduced AHR and methacholine‐induced airway contraction, while blocking 5‐HT2A receptors in wild types eliminated AHR, implying that mast cells contribute to AHR by releasing 5‐HT. Primary mouse and human lung mast cells express muscarinic M3 receptors. Mouse lung mast cells store 5‐HT intracellularly, and methacholine induces release of 5‐HT from lung‐derived mouse mast cells and Ca2+ flux in human LAD‐2 mast cells. Conclusions Methacholine activates mast cells to release 5‐HT, which by acting on 5‐HT2A receptors enhances bronchoconstriction and AHR. Thus, M3‐directed asthma treatments like tiotropium may also act by targeting mast cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mast cell‐derived serotonin enhances methacholine‐induced airway hyperresponsiveness in house dust mite‐induced experimental asthma

Méndez-Enríquez

Alvarado-Vázquez

Abma

et al. 2021

Allergy

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“…We have previously described a rare population of human MCp in the peripheral blood and bone marrow (3,4). Here, human MCp from blood and bone marrow were analyzed for their possible expression of CCR1 and CCR5.…”

Section: Human Mcp Demonstrate Surface Expression Of Ccr1 and Ccr5mentioning

confidence: 99%

“…In adult mice, mast cells seem to have a dual origin with long-lived connective tissue type mast cells mainly originating from yolk sac-derived mast cell progenitors (MCp), and mucosal mast cells developing from bone marrow-derived MCp that originate from fetal hematopoietic stem cells (2). In humans, a MCp population is present in peripheral blood and bone marrow (3,4). Mouse and human MCp are extremely rare, corresponding to ∼0.005% of blood mononuclear cells (5).…”

Section: Introductionmentioning

confidence: 99%

Localization-Specific Expression of CCR1 and CCR5 by Mast Cell Progenitors

et al. 2020

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Mast cells are powerful immune cells found predominately in barrier tissues. They play an important role in immune surveillance and act as effector cells in allergic reactions. Mast cells develop from mast cell progenitors (MCp), which migrate to the peripheral tissues via the blood circulation. Presumably, the homing of MCp to the peripheral sites and localization is regulated by chemotactic signals. Due to the scarce abundance of these cells, chemotactic receptors have not been previously characterized on primary MCp. Here, mRNA transcripts for CCR1 and CX 3 CR1 were identified in mouse bone marrow and lung MCp in a gene expression screen of chemotactic receptors. However, surface expression of CCR1 was only found in the bone marrow MCp. Flow cytometry-based screening identified distinct surface expression of CCR5 by mouse peritoneal mast cells and MCp, while surface expression of CXCR2-5, CX 3 CR1, CCR1-3, CCR6-7, and CCR9 was not detected. Low surface expression of CCR5 was detected in mouse MCp in the bone marrow, spleen, and lung. To translate the findings to human, blood and bone marrow MCp from healthy donors were analyzed for possible CCR1 and CCR5 expression. Human MCp showed distinct surface expression of both CCR1 and CCR5. The expression levels of these chemokine receptors were higher in human bone marrow MCp than in the peripheral blood, suggesting that CCR1 and CCR5 may mediate retention in the bone marrow. In conclusion, mouse and human MCp show differential expression of CCR1 and CCR5 depending on their localization.

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“…Several studies have shown that MFC is a highly sensitive method for detecting and enumerating MCs in the bone marrow (BM), even in samples with very low MC percentage (Sánchez‐Muñoz, Teodosio, Morgado, & Escribano, 2011; Sánchez‐Muñoz, et al, 2014). It has been documented that in the bone marrow, MCs differentiate from the lineage‐specific markers negative (Lin − ), CD34 + , CD38 + , CD117 (c‐KIT) + and HLADR −/+ common myeloid progenitors (CMPs) (Dahlin & Hallgren, 2015; Salomonsson & Ungerstedt, 2020; Schmetzer, Valentin, Church, Maurer, & Siebenhaar, 2016). The MC precursors (immature MCs) differentiating from the CMPs show CD117 +++ , CD34 +/− , CD38 +/− , CD203 −/+ , CD33 ++ , CD45 + HLADR +/− , and tryptase −/+ expression (Escribano et al, 1998; Sánchez‐Muñoz et al, 2011; Teodosio, Garcia‐Montero, Jara‐Acevedo, et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Mast cell differentiation of leukemic blasts in diverse myeloid neoplasms: A potential pre‐myelomastocytic leukemia condition

Panda

Chatterjee

Khanka

et al. 2020

Cytometry Part B Clinical

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Introduction: Myeloid neoplasm with blasts showing mast cell (MC)-differentiation and MC-component less than 10% of all nucleated cells but not fulfilling the criteria for systemic mastocytosis with associated hematological neoplasm (SM-AHN) or myelomastocytic leukemia (MML) has not been described in the literature. Herein, we report a study of diverse myeloid malignancies with blasts showing MCdifferentiation but not meeting the criteria for SM-AHN or MML. We also evaluated the utility of flow-cytometric immunophenotyping (FCI) in the characterization of immature-MCs (iMCs). Methods:We identified nine patients of myeloid neoplasms and studied their morphological, FCI, immunohistochemistry, cytogenetic and molecular characteristics.We also compared the immunophenotypic features of MCs from patient samples with control samples. Results:The study included patients with newly-diagnosed acute myeloid leukemia (n = 4), chronic myelomonocytic leukemia (n = 1), and chronic myeloid leukemia on follow-up (n = 4) showing MC differentiation in leukemic-blasts. These patients had mildly increased MCs (range, 0.5%-3%) in bone-marrow morphology, including immature-forms and did not meet the criteria for either SM-AHN or MML. On FCI, iMCs were positive for bright-CD117, heterogeneous-CD34, dim-to-negative-HLADR, and moderate-CD203c expression. Expression-levels of CD123 and CD38 were higher (p < 0.001) but CD33 and CD45 were lower in iMCs compared to mature-MC from control samples (p = 0.019 and p = 0.0037). Conclusion:We reported a rare finding of MC differentiation of leukemic blasts in diverse myeloid neoplasms and proposed it as a potential pre-myelomastocytic leukemia condition. We described the distinct immunophenotypic signature of immature-MCs using commonly used markers and highlighted the utility of FCI for the diagnosis of this entity.

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Demonstration of human mast cell progenitors in the bone marrow

Abstract: Bifidobacterium longum MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial.

Cited by 7 publications

References 10 publications

Mast cell‐derived serotonin enhances methacholine‐induced airway hyperresponsiveness in house dust mite‐induced experimental asthma

Mast cell‐derived serotonin enhances methacholine‐induced airway hyperresponsiveness in house dust mite‐induced experimental asthma

Localization-Specific Expression of CCR1 and CCR5 by Mast Cell Progenitors

Mast cell differentiation of leukemic blasts in diverse myeloid neoplasms: A potential pre‐myelomastocytic leukemia condition

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