Dual effect of spermine on mast cell secretion exhibits different calcium and temperature requirements

Mast cells release many biologically active molecules upon stimulation by a variety of molecules such as immunoglobulin E: (IgE) and specific antigen, anaphylatoxins, as well as a number of cationic compounds which include dr ugs, kinins and neuropeptides. The effect of the naturally occurring polyam ine spermine was studied because, even though it is polycationic, it has be en implicated in the modulation of secretory processes in a variety of cell s. In particular, it was previously shown that oxidation products of spermi ne inhibit mast cell secretion. High concentrations of spermine (5 x 10(-3) M) added at 37 degrees C induced mast cell secretion that had similar char acteristics with that triggered by compound 48/80 (48/80), However, spermin e inhibited mast cell secretion in a dose-dependent manner as long as it wa s added at 4-10 degrees C for at least 10 min in the absence of Ca++ before warming the cells to 37 degrees C and triggering them with 48/80, These fi ndings were true both for purified rat peritoneal mast cells and for rat sk in mast cells in situ. Addition of calcium after the cells had been warmed to 37 degrees C could not reverse this inhibition. The inhibition seen when spermine was added at 4 degrees C was, however, overcome if phorbol myrist ate acetate (PMA) or NaF, which activate PKC and G proteins respectively, w ere added to mast cells at 37 degrees C together with Ca++. These results i ndicate that polyamines could be important modulators of the activation sta te of mast cells and might help further define the biochemical events invol ved in mast cell secretion, (C) 1999 Published by Elsevier Science Ltd on b ehalf of the International Society for Immunopharmacology. All rights reser ved.