Regulation of immunoglobulin E-mediated secretion by protein phosphatases in human basophils and mast cells of skin and lung

A wide range of serine/threonine protein phosphatase (PP) inhibitors were s tudied for effects on the immunoglobulin E (IgE)-mediated release of histam ine from human lung mast cells, human skin mast cells and basophils. Okadai c acid (OA) inhibited the release of histamine from all three cell types in a concentration-dependent manner. Two structural analogues of okadaic acid , okadaol and okadaone, known to be less active than the parent molecule as inhibitors of PP, were less active than okadaic acid as inhibitors of hist amine release in these three cell types. A number of PP inhibitors, showing differences in selectivity for PP1 and PP2A, were also evaluated. Calyculi n, which is roughly equipotent as a PPI and PP2A inhibitor, attenuated the release of histamine from all three cell types. Similarly, tautomycin (TAU) , which shows greater selectivity for PP1 over PP2A, was also effective at inhibiting histamine release in all three cell types. In contrast, fostriec in, which is very much more potent as an inhibitor of PP2A over PP1, was in effective as an inhibitor in all three cell types. These data indicate that the regulation of mediator release by PPs is similar in lung mast cells, s kin mast cells and basophils. Moreover, the data suggest that PPI is import ant in the control of cellular activity. (C) 2001 Elsevier Science B.V. All rights reserved.