Protein kinase C modulates immunoglobulin e-mediated activation of human mast cells from lung and skin. I. pharmacologic inhibition

W. A. Massey, V. L. Cohan, D. W. MacGlashan, S. W. Gittlen, A. Kagey-Sobotka, L. M. Lichtenstein, J. A. Warner

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)824-829
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume258
Issue number3
StatePublished - 1991

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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