Effect of prostaglandin D2 in modulating histamine release from human basophils

Prostaglandin (PG) D2 is the major cyclooxygenase metabolite of arachidonic acid released after immunologic stimulation of mast cells. In this report, we demonstrate that this PG is unlike other PGs previously investigated in that it enhances human basophil histamine release at concentrations of 1 to 100 nM. Enhancement is seen when antigen, the phorbol diester, 12-O-tetradecanoylphorbol-13-acetate and ionophore A23187 are used to initiate release and, in preparations of basophils, purified to 51 to 66% of total cell number as well as in preparations of mixed leukocytes. This enhancement is a late or "second stage" phenomenon as defined by the two stages of histamine release and is additive with the enhancement produced by D2O, but not with the enhancement produced by indomethacin or 5-hydroperoxyeicosatetraenoic acid. PGD2 also reverses the inhibition of release produced by drugs and hormones such as dimaprit and PGE2 that activate adenylate cyclase to increase cellular cyclic AMP levels. These data suggest that PGD2 may play an important role in allergic and immunologic reactions and suggest a mechanism by which mast cells and basophils can interact during these reactions.