Mast cells represent important sources of vasoactive amines (histamine and, in murine rodents, serotonin), proteoglycans (e.g. heparin), certain proteases, and products of arachidonic acid oxidation. Because mast cells reside in virtually all vascularized tissues, and because they may be triggered to release or generate their mediators in response to stimulation by a wide variety of signals (IgE and specific antigen, complement fragments, immune complexes, basic peptides, T cell products, direct injury, etc.), mast cells have been implicated as critical participants in many immune responses and inflammatory reactions. Yet only one of these proposed functions, the pivotal role of mast cells in IgE-dependent immediate hypersensitivity reactions, has been confirmed beyond reasonable doubt. We therefore wish to use two different varieties of mutant mice that congenitally lack mast cells to investigate directly the specific contributions of mast cells to inflammatory or immune responses in vivo. These mutant mice (W/W-v and S1/S1-d) virtually lack mast cells of both the """"""""connective tissue"""""""" and """"""""mucosal"""""""" types (less than 0.3% the normal level in adult skin, none in most other organs including the stomach) and cannot express conventional mast cell function (e.g., passive cutaneous anaphylaxis). Furthermore, transplantation of normal (+/+) bone marrow cells or cultured, """"""""T cell-dependent"""""""" mast cells into one of these mutants (W/W-v) results in repopulation of the tissues of the recipient mice with both """"""""connective tissue-type"""""""" and """"""""mucosal"""""""" mast cells. We will use these in vivo model systems to test the working hypothesis that the acute consequences of mast cell activation in inflammation and immunity in large part reflect effects of mast cell mediators on the local microvasculature, but that these consequences may vary according to anatomical site and type of mast cells involved in the reaction.

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National Institute of Allergy and Infectious Diseases (NIAID)
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Allergy and Immunology Study Section (ALY)
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Beth Israel Deaconess Medical Center
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