Article

New models for analyzing mast cell functions in vivo

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
Trends in Immunology (Impact Factor: 10.4). 11/2012; 33(12). DOI: 10.1016/j.it.2012.09.008
Source: PubMed

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.

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    • "Human plasma concentrations of tryptase, a MC-specific enzyme, increase with rising body mass index (BMI) (Fenger et al., 2012) and correlate with body fat mass, glycated hemoglobin, fasting insulin level, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) index (Ramalho et al., 2012). Although a recent study using anemic MC-deficient Kit W/Wv mice and Cpa Cre/+ mice that affect more than just MCs (Reber et al., 2012) claimed a negligible role of MCs in obesity and diabetes (Gutierrez et al., 2015), MC stabilizer ketotifen reduces BMI, HbA1c, fasting blood glucose, low-density lipoproteins, and triglyceride, and increases adiponectin and high-density lipoproteins among obese and diabetic patients (El-Haggar et al., 2015). Macrophages (F4/80 + CD11b + ) drive obesity-associated inflammation and diseases. "
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    • "We found that mast cell-deficient W/Wv mice exhibited reduced susceptibility to CIM as compared with WT mice (Figures 3 and 4) and that the reduced susceptibility of W/Wv mice was restored by the reconstitution of mast cells (Figure 6). Although we could not exclude the possibility that other abnormalities of W/Wv mice such as anemia and reduced numbers of neutrophils and basophils [1,26] are also involved in the reduced susceptibility to CIM, our results strongly suggest that mast cells in skeletal muscle play an important role in the development of CIM. "
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    • "However, these strains generally have loss of function mutations in the c-kit – SCF axis, complicating the picture with deficiencies in other c-kit expressing hematopoietic cells. More recently, new mouse models have been developed and will likely give a clearer picture of the functions unique to mast cells (Reber et al., 2012). "
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