Chondroitin sulphate inhibits connective tissue mast cells
Br J Theoharides TC, Patra P, Boucher W, Letourneau R, KempurajD, Chiang G, Jeudy S, Hesse L, Athanasiou A
Pharmacol 2000 Nov;131(6):1039-49
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Mast cells derive from the bone marrow and are responsible forthe development of allergic and possibly inflammatory reactions.Mast cells are stimulated byimmunoglobulin E (IgE) and specificantigen, but also by a number ofneuropeptides such asneurotensin (NT), somatostatin or substance P (SP), to secretenumerous pro-inflammatory molecules that include histamine,cytokines and proteolytic enzymes. Chondroitin sulphate, amajor constituent of connective tissues and of mast cellsecretory granules, had a dose-dependent inhibitory effect on ratperitoneal mast cell release of histamine induced by the mastcellsecretagogue compound 48/80 (48/80). This inhibition wasstronger than that of the clinically available mast cell ”stabilizer”disodium cromoglycate(cromolyn). Inhibition by chondroitinsulphate increased with the length ofpreincubation and persistedafter the drug was washed off, while the effect ofcromolyn waslimited by rapid tachyphylaxis. Immunologic stimulationofhistamine secretion from rat connective tissue mast cells(CTMC) was also inhibited, but this effect was weaker inumbilical cord-derived human mast cells and was absent in ratbasophilic leukemia (RBL) cells which are consideredhomologous to mucosal mast cells (MMC). Oligo- andmonosaccharides were not as effective as the polysaccharides.’, ‘Inhibition, documented by light and electron microscopy,involved a decrease of intracellular calcium ion levels shownbyconfocal microscopy and image analysis. Autoradiography atthe ultrastructurallevel showed that chondroitin sulphate wasmostly associated with plasma andperigranular membranes.Chondroitin sulphate appears to be a potent mast cell inhibitor ofallergic and nonimmune stimulation with potential clinicalimplications.
PMID: 11082109