Jw. Verbsky et al., MAST-CELL ACTIVATION IN HUMAN SYNOVIUM EXPLANTS BY CALCIUM IONOPHORE A23187, COMPOUND-48 80, AND RABBIT IGG ANTI-HUMAN IGE, BUT NOT MORPHINE-SULFATE/, Inflammation research, 45(1), 1996, pp. 35-41
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.