Mast cells mouse models

A Sail, R Matsumoto, HP McNeil, M Karplus, RL Stevens. Three-dimensional models of four mouse mast cell chymases. Identification of proteoglycan-bmdmg regions and protease-specific antigenic epitopes. I Biol Chem 268 9023-9034, 1933. 

This chapter highlights the mechanisms responsible for mast cell activation during anaphylactic responses to environmental substances. In addition to discussing in detail the activation of mast cells and basophils by IgE and antigen, we also will describe how mouse models have been used to analyze the importance of various proteins, cells, mediators and activation mechanisms in the expression of anaphylaxis in that species. 

Although human anaphylaxis is a systemic reaction, the mouse model of passive cutaneous anaphylaxis (PGA) has been used extensively to enhance our understanding of mechanisms which also may contribute to systemic anaphylaxis. Unlike systemic anaphylaxis in the mouse, PGA appears to be entirely dependent on mast cells [4,6]. While IgE appears to be the primary antibody isotype that mediates PCA reactions in actively immunized mice, activation of FcyRIII by a fraction of IgGl antibodies (called anaphylactic IgGl) can also mediate PCA reactions in mice [4]. 

Wang HW, Tedla N, Hunt JE, Wakefield D, McNeil HP. Mast cell accumulation and cytokine expression in the tight skin mouse model of scleroderma. Exp Dermatol 2005 14(4) 295-302. 

The role of mast cells and histamine inducing itch remains unclear in dry skin. It has been shown that histamine concentrations increase 48 hours following acetone treatment in a dry environment.23 A subsequent study demonstrated an increased number of mast cells and histamine levels in the dermis of hairless mice in response to low environmental humidity.46 The authors did not examine a relationship between scratching behavior with the increase in mast cells and histamine. Miyamoto et al. used the mouse model treated with water followed by 1 1 acetone ether to see if they could demonstrate an increase in mast cell number or degranulation however, they found no difference.24 Furthermore, they performed the same study on mast cell deficient mice and were able to induce a similar scratching behavior, which suggests that mast cells may not play a definite role in the mechanism of itch in dry skin. 

The mouse has commonly been utilized as a model for human asthma. The mouse that can be sensitized to a variety of antigens has proven to be a valuable resource in understanding many components of the pathogenesis of asthma in humans. However, the mouse model is not a perfect model as there are differences in degranulation of eosinophils and release of serotonin from mast cells between mice and humans in the mouse model of asthma compared to human asthma. Transgenic mice may be a valuable asset to utilize in understanding pathways and potential realms for therapeutic intervention. 

The rat is also a common model for human asthma and has a size advantage over the mouse, resulting in enhanced ability for collection of blood and bronchoalveolar fluid. The BN rat is the most commonly utihzed strain due to its pronounced IgE and inflammatory response to challenge following sensitization (Hylkema et al., 2002). As is the case with the mouse, rats are not considered a perfect model due to differences in the release of serotonin from mast cells between rats and humans. 

With these differences in mind, we review some of the important findings identified using mouse models of human asthma with specific emphasis on the role of mast cells and IgE. We present published studies and our own data that investigate the role of mast cells and IgE in murine models of allergic inflammation. Finally, we attempt to interpret and reconcile the disparate murine data and put them in context with recent human trials using an anti-IgE antibody. 

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