RT Journal Article
SR Electronic
T1 Protein kinase C modulates immunoglobulin E-mediated activation of human mast cells from lung and skin. I. Pharmacologic inhibition.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 824
OP 829
VO 258
IS 3
A1 W A Massey
A1 V L Cohan
A1 D W MacGlashan, Jr
A1 S W Gittlen
A1 A Kagey-Sobotka
A1 L M Lichtenstein
A1 J A Warner
YR 1991
UL http://jpet.aspetjournals.org/content/258/3/824.abstract
AB It is widely appreciated that protein kinase C (PKC) is activated in a variety of secretory cells after stimulation. By using two complementary pharmacologic approaches, we have investigated the role of PKC in immunoglobulin E (IgE)-mediated secretion from human lung, bronchoalveolar lavage and skin mast cells. We examined the effect of the PKC inhibitor, staurosporine, on goat anti-human IgE-induced mediator release. In lung mast cells, the IC50 for staurosporine on histamine release was 2.8 +/- 1.4 nM (n = 9). The drug was slightly more potent in skin mast cells where the IC50 was 0.64 +/- 2.0 nM (n = 6), but staurosporine had no effect on the IgE-mediated release of histamine from bronchoalveolar lavage mast cells. Mast cells were also incubated overnight with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to down regulate PKC and the response to goat anti-human IgE was measured. Prolonged exposure to 100 ng/ml of TPA reduced IgE-mediated histamine release from 28 +/- 6 to 6 +/- 1% in the skin mast cells whereas similar treatment only reduced the response of lung mast cells from 36 +/- 5 to 26 +/- 6%. Despite using agents which act by different mechanisms, short-term inhibition with staurosporine and long-term treatment with TPA, we obtained consistent results which suggest that PKC is playing a prorelease role in IgE-mediated signaling. Our results also suggest that skin and lung mast cells are more sensitive to PKC down-regulation than bronchoalveolar mast cells. This heterogeneity between human mast cells at the level of PKC regulation of cell activation is previously undescribed.