The long-term goal of our investigation is to understand the function of basophils and mast cells in immunologic reactions of both immediate and delayed-type hypersensitivity in neoplasia, and in normal physiology. Recent progress to this end has been 3-fold: (1) we have identified metachromatic-granulated cells in human peritoneal fluids to have the morphology and release responses diagnostic of basophils--not mast cells; (2) we have clarified the ultrastructural morphology of degranulation of isolated human lung mast cells. We found that anaphylactic degranulation is accompanied by a net decrease in volume of granules, which is preceded by alteration of granule matrix patterns in the absence of granule extrusion to the exterior. By contrast, lipid bodies do not change in net volume during degranulation. Cytoplasmic degranulation channels, formed during release reactions, are rapidly exteriorized and surface membrane is shed, resulting in a net loss of surface membrane area. By contrast, nuclear membrane remains constant. We have utilized a sophisticated morphometric analysis to show that the mechanism of generation of mast cell granules is distinctive and multimodal and is different from that of lipid bodies, which is unimodal. Finally, we demonstrated the uniqueness of cytoplasmic granules from lipid bodies by EM autoradiography. Thus, granules incorporated radiolabelled sulfur, not arachidonic acid, whereas lipid bodies incorporated radiolabelled arachidonic acid, not sulfur; and (3) we showed that H?3? arachidonic acid-labelled cytoplasmic lipid bodies in macrophages of three species: mouse, man, and guinea pig. (SR)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA028834-07
Application #
3168363
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1980-03-01
Project End
1987-03-31
Budget Start
1986-03-01
Budget End
1987-03-31
Support Year
7
Fiscal Year
1986
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) 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
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

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