Differential effect of flavonoids on inhibition of secretion and accumulation of secretory granules in rat basophilic leukemia cells

Rat basophilic leukemia (RBL) cells resemble mucosal mast cells (MMC) and d evelop few secretory granules under normal culture conditions. RBL cells ha ve been used for the study of secretion and for the possible involvement of MMC in food allergies and irritable bowel syndrome (IBS). The flavonoid qu ercetin is one of very few molecules that inhibit RBL cell proliferation an d constitutive histamine release; it also induces synthesis of rat mast cel l protease (RMCP) II and accumulation of secretory granules. Even though qu ercetin is available as a food supplement over the counter, some early stud ies had indicated it may be carcinogenic. We, therefore, compared the effec t of quercetin to that of other flavonoids with similar structure. Flavone, kaempferol, myricetin and morin were investigated for their action on RBL cell secretion of beta-hexosaminidase stimulated by anti-DNP serum and DNP- BSA, as well as on secretory granule development. Quercetin, myricetin and kaempferol inhibited RBL cell secretion significantly only at 10(-4) M, Fla vone inhibited secretion at 10(-4), 10(-5) and 10(-6) M; it also maximally induced secretory granule accumulation as evidenced by light and electron m icroscopy. In contrast, morin which differs structurally only by one extra hydroxyl group had minimal effect. These results indicate that flavone is c apable of inhibiting stimulated secretion and inducing secretory granule de velopment at reasonable concentrations. (C) 1999 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.