Differentiation of second messenger systems in mast cell activation.
Pretreatment of rat peritoneal mast cells with either Staurosporine or an analog K-252a, lead to a dose-related inhibition of histamine release when stimulated with Anti-IgE (IC50: Staurosporine = 110 nM; K-252a = 100 nM). In contrast, the two PKC inhibitors (1-1000 nM) failed to inhibit histamine release induced by compound 48/80 (0.5-1 micrograms/ml). Exposure of Anti-Asc-IgE sensitized mouse bone marrow derived mast cells to Asc-BSA lead to the release of both histamine (510 ng +/- 12.6 ng/10(6) cells) and immunoreactive Leukotriene C4 (27.0 +/- 12.6 ng/10(6) cells). LTC4 release was inhibited by Staurosporine and K-252a with an IC50 of 75 nM for both compounds. Pretreatment of rat peritoneal mast cells with PMA 100 nM lead to a small but significant release of histamine (18.3 +/- 3.6%). Pretreatment of these cells with K-252a or Staurosporine lead to a dose related inhibition of histamine release with an ED50 of 10 nM for Staurosporine and 60 nM for K-252a. Treatment of rat peritoneal mast cells with the calcium ionophore A23187 lead to a significant release of histamine which was not inhibited by either of the two kinase inhibitors (0.1-1000 nM). The two kinase inhibitors also inhibited mouse bone marrow derived mast cell proliferation in response to IL-3 with IC50 of 80 nM for Staurosporine and 270 nM for K-252a.
White
J R
JR
Dept. of Immunology, Smith Kline and French Labs, King of Prussia, PA 19406-0939.
Zembryki
D
D
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D000001:Calcimycin / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D007073:Immunoglobulin E / Q000276:immunology; D026121:Indole Alkaloids; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D013189:SRS-A / Q000378:metabolism; D015290:Second Messenger Systems; D019311:Staurosporine
D000470:Alkaloids; D000888:Antibodies, Anti-Idiotypic; D002227:Carbazoles; D026121:Indole Alkaloids; D013189:SRS-A; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D000001:Calcimycin; C049985:staurosporine aglycone; D011493:Protein Kinase C; D019311:Staurosporine