Chondroitin sulphate inhibits connective tissue mast cells

1 Mast cells derive from the bone marrow and are responsible for the develo pment of allergic and possibly inflammatory reactions. Mast cells are stimu lated by immunoglobulin E (IgE) and specific antigen, but also by a number of neuropeptides such as neurotensin (NT), somatostatin or substance P (SP) , to secrete numerous pro-inflammatory molecules that include histamine, cy tokines and proteolytic enzymes. 2 Chondroitin sulphate, a major constituent of connective tissues and of ma st cell secretory granules, had a dose-dependent inhibitory effect on rat p eritoneal mast cell release of histamine induced by the mast cell secretago gue compound 48/80 (48/80). This inhibition was stronger than that of the c linically available mast cell 'stabilizer' disodium cromoglycate (cromolyn) . Inhibition by chondroitin sulphate increased with the length of preincuba tion and persisted after the drug was washed off, while the effect of cromo lyn was limited by rapid tachyphylaxis. 3 Immunologic stimulation of histamine secretion from rat connective tissue mast cells (CTMC) was also inhibited, but this effect was weaker in umbili cal cord-derived human mast cells and was absent in rat basophilic leukemia (RBL) cells which are considered homologous to mucosal mast cells (MMC). O ligo- and monosaccharides were not as effective as the polysaccharides. 4 Inhibition, documented by light and electron microscopy, involved a decre ase of intracellular calcium ion levels shown by confocal microscopy and im age analysis. Autoradiography at the ultrastructural level showed that chon droitin sulphate was mostly associated with plasma and perigranular membran es. 5 Chondroitin sulphate appears to be a potent mast cell inhibitor of allerg ic and nonimmune stimulation with potential clinical implications.