1 A variety of chymotryptic substrates and inhibitors prevented the re
lease of histamine and prostaglandin D-2 from rat peritoneal mast cell
s stimulated with anti-IgE but not the calcium ionophore A23187 or a v
ariety of polyamines. 2 The activity of the compounds was strikingly i
ncreased in cells reversibly permeabilized with ATP, indicating the im
portance of their effective incorporation into the cytosol. 3 The comp
ounds produced a comparable inhibition of immunological, but not pharm
acological, histamine release from human mast cells and basophils. 4 T
reatment of rat mast cells with anti-IgE led to a marked increase in t
he total chymotryptic activity expressed by the cells. 5 Immunological
, but not pharmacological, stimulation of permeabilized rat mast cells
loaded with a fluorescent chymotryptic substrate led to a pronounced
and rapid increase in fluorescence, indicating activation of the enzym
e and hydrolysis of the substrate. These changes were attenuated by ch
ymotryptic inhibitors. 6 In total, these data provide compelling evide
nce for the direct involvement of a serine protease in IgE-mediated hi
stamine release from mast cells.