PMID- 1716311
OWN - NLM
STAT- MEDLINE
DCOM- 19911017
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 258
IP  - 3
DP  - 1991 Sep
TI  - Protein kinase C modulates immunoglobulin E-mediated activation of human mast 
      cells from lung and skin. I. Pharmacologic inhibition.
PG  - 824-9
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.
FAU - Massey, W A
AU  - Massey WA
AD  - Division of Clinical Immunology, Johns Hopkins Asthma and Allergy Center, 
      Baltimore, Maryland.
FAU - Cohan, V L
AU  - Cohan VL
FAU - MacGlashan, D W Jr
AU  - MacGlashan DW Jr
FAU - Gittlen, S W
AU  - Gittlen SW
FAU - Kagey-Sobotka, A
AU  - Kagey-Sobotka A
FAU - Lichtenstein, L M
AU  - Lichtenstein LM
FAU - Warner, J A
AU  - Warner JA
LA  - eng
GR  - AI07290/AI/NIAID NIH HHS/United States
GR  - AI08270/AI/NIAID NIH HHS/United States
GR  - AI20253/AI/NIAID NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Alkaloids)
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Arachidonic Acids)
RN  - 0 (anti-IgE antibodies)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 37H9VM9WZL (Calcimycin)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - H88EPA0A3N (Staurosporine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Alkaloids/pharmacology
MH  - Antibodies, Anti-Idiotypic/pharmacology
MH  - Arachidonic Acid
MH  - Arachidonic Acids/metabolism
MH  - Bronchoalveolar Lavage Fluid/cytology/enzymology
MH  - Calcimycin/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Histamine Release/drug effects
MH  - Humans
MH  - Immunoglobulin E/immunology/pharmacology/*physiology
MH  - Lung/cytology/drug effects/*enzymology
MH  - Mast Cells/drug effects/*enzymology
MH  - Protein Kinase C/*antagonists & inhibitors/metabolism/physiology
MH  - Signal Transduction/drug effects/physiology
MH  - Skin/cytology/drug effects/*enzymology
MH  - Staurosporine
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Time Factors
EDAT- 1991/09/11 19:15
MHDA- 2001/03/28 10:01
CRDT- 1991/09/11 19:15
PHST- 1991/09/11 19:15 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1991/09/11 19:15 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1991 Sep;258(3):824-9.