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 studied for effects on the immunoglobulin E (IgE)-mediated release of histamine from human lung mast cells, human skin mast cells and basophils. Okadaic 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 histamine release in these three cell types. A number of PP inhibitors, showing differences in selectivity for PP1 and PP2A, were also evaluated. Calyculin, which is roughly equipotent as a PP1 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, fostriecin, which is very much more potent as an inhibitor of PP2A over PP1, was ineffective 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, skin mast cells and basophils. Moreover, the data suggest that PP1 is important in the control of cellular activity.
Bastan
R
R
Section of Molecular Pharmacology and Pharmacogenetics, University of Sheffield, The Royal Hallamshire Hospital (Floor L), Glossop Road, S10 2JF, Sheffield, UK.
Peirce
M J
MJ
Peachell
P T
PT
D000475:Alkenes / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D008168:Lung / Q000187:drug effects*; D008387:Marine Toxins; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011090:Polyenes; D011714:Pyrans; D011753:Pyrones; D012867:Skin / Q000187:drug effects*; D013141:Spiro Compounds
D000475:Alkenes; D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D010080:Oxazoles; D011090:Polyenes; D011714:Pyrans; D011753:Pyrones; D013141:Spiro Compounds; C053079:tautomycin; D019319:Okadaic Acid; D007073:Immunoglobulin E; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; C040313:fostriecin