MAST-CELL ACTIVATION IN HUMAN SYNOVIUM EXPLANTS BY CALCIUM IONOPHORE A23187, COMPOUND-48 80, AND RABBIT IGG ANTI-HUMAN IGE, BUT NOT MORPHINE-SULFATE/

To investigate human synovial mast cell physiology, we developed a mod el in which mast cells in human synovial explant cultures were activat ed by immunologic or non-immunologic mechanisms. Small (3 mm) cubes of synovial membrane were incubated with or without secretagogue for 30, 45 or 60 min, and supernatant histamine concentrations were quantifie d. We measured significant histamine release with compound 48/80 at co ncentrations greater than or equal to 1 mg/ml, and with calcium ionoph ore A23187 at greater than or equal to 5 mu g/ml. Rabbit IgG anti-huma n IgE induced significant histamine release at all concentrations test ed, maximum at 78 mu g/ml. Morphine sulfate produced no histamine rele ase from synovial explants, in contrast to its significant stimulation of histamine release from neonatal foreskin explants in our explant s ystem. We confirmed synovial mast cell degranulation by electron micro scopy, and showed that it corresponded with measurable histamine relea se. Furthermore, histamine release was not due to secretagogue-induced cytotoxicity, as assessed by supernatant lactate dehydrogenase levels and by ultrastructural analysis. Since morphine sulfate induces mast cell degranulation and histamine release in adult and neonatal human s kin, our data show that although synovial and dermal mast cells have a similar granule enzyme profile and electron microscopic morphology, t hey differ in functional responses. These observations support recent data that among similar human mast cell subtypes there are physiologic differences. Finally, our explant model will be useful in studies of mast cell involvement in arthritis.