Gurish MF, Boyce JAMast cells: ontogeny, homing, and recruitment of a unique innate effector cell. J Allergy Clin Immun 117:1285-1291

Harvard University, Cambridge, Massachusetts, United States
Journal of Allergy and Clinical Immunology (Impact Factor: 11.48). 07/2006; 117(6):1285-91. DOI: 10.1016/j.jaci.2006.04.017
Source: PubMed


Mast cells (MCs) are found principally in peripheral tissues yet are of bone marrow origin. Recent studies in mice trace the MC lineage from the common myeloid progenitor through the granulocyte-macrophage progenitor in the bone marrow to a committed MC progenitor (MCP). Additionally, at least in the mouse, a bipotent basophil-MC progenitor has been identified in the spleen, suggesting a physiologic role for this organ in MC development. MCPs are especially abundant in the mouse intestine, likely ensuring the capacity for a rapid expansion of MCs in the intestinal epithelium during the effector response to helminth infection and perhaps providing a pool of committed cells capable of redistribution to other tissues. Migration of MCPs to the intestine is constitutive and controlled by alpha chemokine receptor 2 and alpha4beta7 integrins expressed on the MCPs, with the latter integrin interacting with endothelial vascular cell adhesion molecule 1 and mucosal addressin cell adhesion molecule 1. In contrast, normal mouse lung tissue contains few MCPs and MCs, and these cellular reservoirs are not affected by the lack of alpha chemokine receptor 2 or alpha4beta7 integrin. Nonetheless, robust recruitment of MCPs to the lung occurs during experimentally induced allergic pulmonary inflammation and requires alpha4beta7 and alpha4beta1 integrins interacting with vascular cell adhesion molecule 1 but not with mucosal addressin cell adhesion molecule 1. Thus although MCs are present in all organs, the pathways responsible for the trafficking of MCPs from the circulation are organ specific and include both constitutive and inducible systems, ensuring both resident MCs and the potential for incremental recruitment in accord with the requirements of the immune response. These findings in mice await confirmation in human subjects.

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    • ". SCF participates in each stage of growth and differentiation of MCs including differentiation, proliferation, chemotaxis, adhesion, and survival [81]. It has been suggested that this global influence of SCF results in the ubiquitous presence of MCs [82]. There are numerous growth and differentiation factors other than SCF, which have been shown to affect MC functions including several of the type 2 helper T cell cytokines [83]. "
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    ABSTRACT: Despite years of intensive investigation that has been made in understanding prostate cancer, it remains one of the major men's health issues and the leading cause of death worldwide. It is now ascertained that prostate cancer emerges from multiple spontaneous and/or inherited alterations that induce changes in expression patterns of genes and proteins that function in complex networks controlling critical cellular events. It is now accepted that several innate and adaptive immune cells, including T- and B-lymphocytes, macrophages, natural killer cells, dendritic cells, neutrophils, eosinophils, and mast cells (MCs), infiltrate the prostate cancer. All of these cells are irregularly scattered within the tumor and loaded with an assorted array of cytokines, chemokines, and inflammatory and cytotoxic mediators. This complex framework reflects the diversity in tumor biology and tumor-host interactions. MCs are well-established effector cells in Immunoglobulin-E (Ig-E) associated immune responses and potent effector cells of the innate immune system; however, their clinical significance in prostate cancer is still debated. Here, these controversies are summarized, focusing on the implications of these findings in understanding the roles of MCs in primary prostate cancer.
    Disease markers 11/2013; 35(6):711-720. DOI:10.1155/2013/478303 · 1.56 Impact Factor
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    • "Mast cells (MCs) are abundant in tissues exposed to the external environment including the skin, intestinal tract, and trachea, and also normally present in heart, lymph nodes, spleen, and CNS [3]. Classically, MCs have been described as essential effector cells of immediate hypersensitivity and chronic allergic reactions that contribute to asthma, atopic dermatitis, and other allergic diseases [4]. Recent findings indicate that MCs are more functionally diverse than previously described. "
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    ABSTRACT: The role of mast cells (MCs) in Toxoplasma gondii infection is poorly known. Kunming outbred mice were infected intraperitoneally with RH strain T. gondii, either treated with compound 48/80 (C48/80, MC activator) or disodium cromoglycate (DSCG, MC inhibitor). Compared with infected controls, infected mice treated with C48/80 exhibited significantly increased inflammation in the liver (P < 0.01), spleen (P < 0.05), and mesentery (P < 0.05) tissues, higher parasite burden in the peritoneal lavage fluids (P < 0.01), and increased levels of mRNA transcripts of T. gondii tachyzoite surface antigen 1 (SAG1) gene in the spleen and liver tissues (P < 0.01), accompanied with significantly increased Th1 cytokine (IFN-γ, IL-12p40, and TNF-α) (P < 0.01) and decreased IL-10 (P < 0.01) mRNA expressions in the liver, and increased IFN-γ (P < 0.01) and IL-12p40 (P < 0.01) but decreased TNF-α (P < 0.01) and IL-4 (P < 0.01) in the spleens of infected mice treated with C48/80 at day 9-10 p.i. Whereas mice treated with DSCG had significantly decreased tissue lesions (P < 0.01), lower parasite burden in the peritoneal lavage fluids (P < 0.01) and decreased SAG1 expressions in the spleen and liver tissues (P < 0.01), accompanied with significantly increased IFN-γ (P < 0.01) and IL-12p40 (P < 0.05) in the liver, and decreased IFN-γ (P < 0.05) and TNF-α (P < 0.01) in the spleens; IL-4 and IL-10 expressions in both the spleen and liver were significantly increased (P < 0.01) in the infected mice treated with DSCG. These findings suggest that mediators associated with the MC activation may play an important role in modulating acute inflammatory pathogenesis and parasite clearance during T. gondii infection in this strain of mice. Thus, MC activation/inhibition mechanisms are potential novel targets for the prevention and control of T. gondii infection.
    PLoS ONE 10/2013; 8(10):e77327. DOI:10.1371/journal.pone.0077327 · 3.23 Impact Factor
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    • "MCs are stem cell factor (SCF)-dependent hematopoietic cells that are ubiquitously distributed throughout the body [18], [19] and initiate inflammatory responses to allergens and infectious agents. They play an important role in triggering exacerbations of asthma through the elaboration of several soluble inflammatory mediators including cys-LTs, histamine, serine proteases, multiple cytokines and chemokines. "
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    ABSTRACT: Cysteinyl leukotrienes (cys-LTs) are a group of lipid mediators that are potent bronchoconstrictors, powerful inducers of vascular leakage and potentiators of airway hyperresponsiveness. Cys-LTs play an essential role in asthma and are synthesized as well as activated in mast cells (MCs). Cys-LTs relay their effects mainly through two known GPCRs, CysLT1R and CysLT2R. Although protein kinase C (PKC) isoforms are implicated in the regulation of CysLT1R function, neither the role of PKCs in cys-LT-dependent MC inflammatory signaling nor the involvement of specific isoforms in MC function are known. Here, we show that PKC inhibition augmented LTD4 and LTE4-induced calcium influx through CysLT1R in MCs. In contrast, inhibition of PKCs suppressed c-fos expression as well MIP1β generation by cys-LTs. Interestingly, cys-LTs activated both PKCα and PKCε isoforms in MC. However, knockdown of PKCα augmented cys-LT mediated calcium flux, while knockdown of PKCε attenuated cys-LT induced c-fos expression and MIP1β generation. Taken together, these results demonstrate for the first time that cys-LT signaling downstream of CysLT1R in MCs is differentially regulated by two distinct PKCs which modulate inflammatory signals that have significant pathobiologic implications in allergic reactions and asthma pathology.
    PLoS ONE 08/2013; 8(8):e71536. DOI:10.1371/journal.pone.0071536 · 3.23 Impact Factor
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