THE EFFECT OF METHYLTRANSFERASE INHIBITORS ON HISTAMINE-RELEASE FROM HUMAN DISPERSED LUNG MAST-CELLS ACTIVATED WITH ANTI-HUMAN IGE AND CALCIUM IONOPHORE A23187

Inhibitors of adenosylmethionine (AdoMet)-dependent methyltransferases reduce histamine release from enzymatically dispersed human lung mast cells activated with either anti-human IgE or calcium ionophore A23187. The IC25 [25% inhibitory concentration] values for adenosine and 3-deazaadenosine (DZA) inhibiting anti-IgE-induced histamine release were 395 and 301 .mu.M respectively. The addition of homocysteine thiolactone (Hcy) potentiated the effects of adenosine and DZA, reducing their IC25 values to 32 M and 10.5 .mu.M, respectively. The adenosine deaminase (adenosine aminohydrolase EC 3.5.4.4) inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) inhibited anti-IgE-induced histamine release with an IC50 of 162 .mu.M. This inhibition was not potentiated by Hcy. The combination of DZA and Hcy effectively inhibited histamine release induced by concentrations of A23187 which released a similar amount of histamine to anti-IgE. The combination was 17 times less potent against A23187-compared with anti-IgE-induced release. AdoMet-dependent methyltransferases apparently play an important role in IgE-dependent histamine release from human lung mast cells but their role in A23187-induced release is less clear. [The IgE-dependent activation of mast cells and basophils initiates a series of membrane and cytoplasmic events which culminate in the non-cytotoxic release of preformed and newly generated mediators of inflammation.].