Basophils and mast cells represent an important source of several inflammatory mediators, certain of which (e.g., histamine, serotonin) are stored in the cells' cytoplasmic granules. Morphologic studies have demonstrated that basophils and/or mast cells are increased in numbers and/or exhibit activation during many different immunologic or pathologic processes in both experimental animals and man. Along with other lines of evidence, these observations indicate that basophils and mast cells participate in a wide variety of biological responses. Previous work in our laboratory has suggested that certain of the important biological functions of basophils and mast cells are mediated by a bidirectional flow of small, membrane bound cytoplasmic vesicles between the plasma membrane and the cytoplasmic granules. Such functions include the internalization of ligands bound to the cell surface, the uptake (and, later, release) of potentially toxic exogenous basic compounds, and the sustained and/or low level release of granule-associated mediators. We now wish to test this model rigorously, with an approach that utilizes a new method of microwave energy-assisted ultrafast fixation recently developed in our laboratory, as well as ultrastructural cytochemistry/immunocytochemistry, high resolution autoradiography, and computer-assisted morphometry. The role of cytoplasmic vesicles will be evaluated in the following phenomena: 1) The uptake, granule storage and release of horseradish peroxidase or eosinophil peroxidase by guinea pigs basophils and rat and mouse mast cells; (2) The stimulation of rat or mouse mast cells with gold-labeled monoclonal IgE and specific antigen, (and the relationship of such stimulation to internalization of IgE-antigen complexes); 3) The release of granule associated histamine (guinea pig basophils, and rat and mouse mast cells) and chymase (rat peritoneal cell) by various concentrations of degranulation stimuli, including IgE and antigen and certain basic compounds; 4) The uptake and release of 3H-serotonin by cloned mouse mast cells and rat peritoneal mast cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA028834-09
Application #
3168364
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1980-03-01
Project End
1992-02-28
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
9
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Nakano, Toru; Sonoda, Takashi; Hayashi, Chieko et al. (2009) Pillars article: fate of bone marrow-derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient w/wv mice. Evidence that cultured mast cells can give rise to both connective tissue type J Immunol 183:6863-81
Dvorak, Ann M (2005) Cyclooxygenase, a key enzyme family for production of prostaglandins, is present in human mast cell lipid bodies. Chem Immunol Allergy 85:68-71
Dvorak, Ann M (2005) Mast cell secretory granules and lipid bodies contain the necessary machinery important for the in situ synthesis of proteins. Chem Immunol Allergy 85:252-315
Dvorak, Ann M (2005) Subcellular localization of the cytokines, basic fibroblast growth factor and tumor necrosis factor-alpha in mast cells. Chem Immunol Allergy 85:72-88
Dvorak, Ann M (2005) Degranulation and recovery from degranulation of basophils and mast cells. Chem Immunol Allergy 85:205-51
Dvorak, Ann M (2005) Mast cell-derived mediators of enhanced microvascular permeability, vascular permeability factor/vascular endothelial growth factor, histamine, and serotonin, cause leakage of macromolecules through a new endothelial cell permeability organelle, the vesic Chem Immunol Allergy 85:185-204
Dvorak, Ann M (2005) Ultrastructural analysis is necessary and sufficient for identification of basophils and mast cells. Chem Immunol Allergy 85:10-67
Dvorak, Ann M (2005) Piecemeal degranulation of basophils and mast cells is effected by vesicular transport of stored secretory granule contents. Chem Immunol Allergy 85:135-84
Dvorak, Ann M (2005) Ultrastructural enzyme-affinity-gold and inhibitor-gold techniques identify subcellular sites of histamine and heparin in basophils and mast cells. Chem Immunol Allergy 85:98-134
Dvorak, Ann M (2005) Immunogold ultrastructural techniques identify subcellular sites of chymase, Charcot-Leyden crystal protein, and histamine in basophils and mast cells. Chem Immunol Allergy 85:89-97

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