An essential role of prostaglandin E on mouse mast cell induction.
We previously established a system for induction of mucosal-type mast cells from mouse spleen cells by long term culture without exogenous IL-3. FCS was important and was able to be divided into mast cell-inducible and non-mast cell-inducible sera. LPS contaminated in FCS was responsible for the mast cell induction. However, we unexpectedly found that both supernatants recovered from the cultures with mast cell-inducible and non-mast cell-inducible sera contained endogenous IL-3. Furthermore, addition of rIL-3 to the cultures with non-mast cell-inducible sera had no effect or induced only a small number of mast cells. This indicates that IL-3 alone is not enough for mast cell induction and that some inflammatory factor(s) induced by LPS is also essential. Prostaglandin E1 (PGE1) and PGE2 induced mast cells in a dose-dependent manner when added into the cultures. The activity of LPS for mast cell induction was inhibited by indomethacin. However, indomethacin failed to inhibit the mast cell induction by exogenous PGE. Exogenous PGE antagonized the indomethacin-induced inhibition of mast cell induction by LPS. Cholera toxin and dibutyryl cyclic AMP (cAMP) also induced mast cells. The A and B subunits of cholera toxin, PGF2 alpha, PGD2, and dibutyryl cGMP failed to induce mast cells. Furthermore, mast cell induction by PGE was dose-dependently suppressed by inhibitors for cAMP-dependent A kinase. The above results show that for mast cell induction, IL-3 needs the cooperation of PGE or other stimulants that can elevate the production of the second messenger cAMP in mast cell precursors.
Hu
Z Q
ZQ
Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, Japan.
Asano
K
K
Seki
H
H
Shimamura
T
T
D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D015230:Prostaglandin D2 / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*
D007377:Interleukin-3; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D002772:Cholera Toxin; D015237:Dinoprost; D017868:Cyclic AMP-Dependent Protein Kinases; D015230:Prostaglandin D2