Chondroitin sulphate inhibits connective tissue mast cells

Abstract

1 Mast cells derive from the bone marrow and are responsible for the development of allergic and possibly in¯ammatory reactions. Mast cells are stimulated by immunoglobulin E (IgE) and speci®c antigen, but also by a number of neuropeptides such as neurotensin (NT), somatostatin or substance P (SP), to secrete numerous pro-in¯ammatory molecules that include histamine, cytokines and proteolytic enzymes. 2 Chondroitin sulphate, a major constituent of connective tissues and of mast cell secretory granules, had a dose-dependent inhibitory eect on rat peritoneal mast cell release of histamine induced by the mast cell secretagogue compound 48/80 (48/80). This inhibition was stronger than that of the clinically available mast cell`stabilizer' disodium cromoglycate (cromolyn). Inhibition by chondroitin sulphate increased with the length of preincubation and persisted after the drug was washed o, while the eect of cromolyn was limited by rapid tachyphylaxis. 3 Immunologic stimulation of histamine secretion from rat connective tissue mast cells (CTMC) was also inhibited, but this eect was weaker in umbilical cord-derived human mast cells and was absent in rat basophilic leukemia (RBL) cells which are considered homologous to mucosal mast cells (MMC). Oligo-and monosaccharides were not as eective as the polysaccharides. 4 Inhibition, documented by light and electron microscopy, involved a decrease of intracellular calcium ion levels shown by confocal microscopy and image analysis. Autoradiography at the ultrastructural level showed that chondroitin sulphate was mostly associated with plasma and perigranular membranes.5 Chondroitin sulphate appears to be a potent mast cell inhibitor of allergic and nonimmune stimulation with potential clinical implications.

A Pilot Open Label Study of Cystoprotek® in Interstitial Cystitis

“…Chondroitin sulfate has been used, together with its building block glucosamine, for the treatment of osteoarthritis, with potential benefit as indicated by a recent meta-analysis. Moreover, preincubation of rat peritoneal mast cells for 10 min with chondroitin sulfate resulted in 76.5% inhibition of histamine release (p=0.0004) (16). In contrast, the inhibitory action of the "mast cell stabilizer" drug cromolyn decreased rapidly if preincubation lasted for more than 1 min 14.3 ± 2.9* (16).…”

“…Moreover, preincubation of rat peritoneal mast cells for 10 min with chondroitin sulfate resulted in 76.5% inhibition of histamine release (p=0.0004) (16). In contrast, the inhibitory action of the "mast cell stabilizer" drug cromolyn decreased rapidly if preincubation lasted for more than 1 min 14.3 ± 2.9* (16). The inhibitory effect of chondroitin sulfate extended to stimulation of mast cells by the neuropeptide SP, as well as by immunoglobulin E and anti-IgE, and was correlated with its inhibitory effect on intracellular calcium ion levels.…”

“…The beneficial effect of the glycosaminoglycans may also derive from inhibition of bladder mast cell activation, since both PPS (15) and chondroitin sulfate were (16) shown to inhibit mast cell activation amply documented in IC bladders (3).…”

Effects of Proteoglycan on Dextran Sulfate Sodium-Induced Experimental Colitis in Rats

“…Inflammatory conditions, such as necrotizing enterocolitis and inflammatory bowel diseases, result in a loss of CS in the mucosa [3,4]. It is also postulated that CS partially inhibits leukocyte elastase activity and inhibits connective tissue mast cells [5,6]. CS is used as a safe drug in patients with osteoarthritis [7].…”

Chondroitin Sulfate Intake Inhibits the IgE-mediated Allergic Response by Down-regulating Th2 Responses in Mice

“…Recently, there have been a number of reports on the biochemical activities of orally administrated exogenous CS, including its anti-inflammatory and chondroprotective properties (12)(13)(14)(15)(16)(17)(18)(19). It has been proposed that these activities result from an increase in the biosynthesis of connective tissue components, such as hyaluronan, at disease sites (20,21). Both in vitro and in vivo studies have shown that CS regulates the formation of new cartilage by stimulating the chondrocyte synthesis of collagen, proteoglycans and hyaluronan (22,23).…”