New models for analyzing mast cell functions in vivo
ABSTRACT In addition to their well-accepted role as critical effector cells in anaphylaxis and other acute IgE-mediated allergic reactions, mast cells (MCs) have been implicated in a wide variety of processes that contribute to disease or help to maintain health. Although some of these roles were first suggested by analyses of MC products or functions in vitro, it is critical to determine whether, and under which circumstances, such potential roles actually can be performed by MCs in vivo. This review discusses recent advances in the development and analysis of mouse models to investigate the roles of MCs and MC-associated products during biological responses in vivo, and comments on some of the similarities and differences in the results obtained with these newer versus older models of MC deficiency.
SourceAvailable from: Riccardo Sibilano[Show abstract] [Hide abstract]
ABSTRACT: Mast cells (MCs) are cells of hematopoietic origin that normally reside in mucosal tissues, often near epithelial cells, glands, smooth muscle cells, and nerves. Best known for their contributions to pathology during IgE-associated disorders such as food allergy, asthma, and anaphylaxis, MCs are also thought to mediate IgE-associated effector functions during certain parasite infections. However, various MC populations also can be activated to express functional programs-such as secreting preformed and/or newly synthesized biologically active products-in response to encounters with products derived from diverse pathogens, other host cells (including leukocytes and structural cells), damaged tissue, or the activation of the complement or coagulation systems, as well as by signals derived from the external environment (including animal toxins, plant products, and physical agents). In this review, we will discuss evidence suggesting that MCs can perform diverse effector and immunoregulatory roles that contribute to homeostasis or pathology in mucosal tissues.Mucosal Immunology advance online publication, 11 February 2015; doi:10.1038/mi.2014.131.Mucosal Immunology 02/2015; DOI:10.1038/mi.2014.131 · 7.54 Impact Factor
Article: The role of mast cells in cancers[Show abstract] [Hide abstract]
ABSTRACT: Mast cells are immune cells that accumulate in the tumors and their microenvironment during disease progression. Mast cells are armed with a wide array of receptors that sense environment modifications and, upon stimulation, they are able to secrete several biologically active factors involved in the modulation of tumor growth. For example, mast cells are able to secrete pro-angiogenic and growth factors but also pro- and anti-inflammatory mediators. Recent studies have allowed substantial progress in understanding the role of mast cells in tumorigenesis/disease progression but further studies are necessary to completely elucidate their impact in the pathophysiology of cancer. Here we review observations suggesting that mast cells could modulate tumor growth in humans. We also discuss the drawbacks related to observations from mast cell-deficient mouse models, which could have consequences in the determination of a potential causative relationship between mast cells and cancer. We believe that the understanding of the precise role of mast cells in tumor development and progression will be of critical importance for the development of new targeted therapies in human cancers.01/2015; 7:09. DOI:10.12703/P7-09
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ABSTRACT: Graphical Abstract Highlights d Obesity and insulin resistance are unaffected by mast cell deficiency d Global Kit deficiency protects mice from obesity and associated metabolic disorders d Reconstitution of Kit mutant mice with Kit +/+ HSCs normalizes metabolic phenotype In Brief Mice with Kit mutations have several immune and non-immune abnormalities, including mast cell deficiency, and are protected from weight gain and insulin resistance during diet-induced obesity. Gutierrez et al. show that this protection is not mediated by mast cell deficiency, as previously thought, but instead through hematopoietic Kit deficiency.