Differential release of mast cell mediators and the pathogenesis of inflammation.
Mast cells are well known for their involvement in allergic and anaphylactic reactions, during which immunoglobulin E (IgE) receptor (Fc epsilon RI) aggregation leads to exocytosis of the content of secretory granules (1000 nm), commonly known as degranulation, and secretion of multiple mediators. Recent findings implicate mast cells also in inflammatory diseases, such as multiple sclerosis, where mast cells appear to be intact by light microscopy. Mast cells can be activated by bacterial or viral antigens, cytokines, growth factors, and hormones, leading to differential release of distinct mediators without degranulation. This process appears to involve de novo synthesis of mediators, such as interleukin-6 and vascular endothelial growth factor, with release through secretory vesicles (50 nm), similar to those in synaptic transmission. Moreover, the signal transduction steps necessary for this process appear to be largely distinct from those known in Fc epsilon RI-dependent degranulation. How these differential mast cell responses are controlled is still unresolved. No clinically available pharmacological agents can inhibit either degranulation or mast cell mediator release. Understanding this process could help develop mast cell inhibitors of selective mediator release with novel therapeutic applications.
Theoharides
Theoharis C
TC
Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts - New England Medical Center, Boston, MA, USA. theoharis.theoharides@tufts.edu
Kempuraj
Duraisamy
D
Tagen
Michael
M
Conti
Pio
P
Kalogeromitros
Dimitris
D
D015306:Biogenic Monoamines / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology*; D010455:Peptides / Q000378:metabolism
D015306:Biogenic Monoamines; D004798:Enzymes; D018836:Inflammation Mediators; D010455:Peptides