Document 0109
 DOCN  M9550109
 TI    IL-4 renders mast cells functionally responsive to endothelin-1.
 DT    9505
 AU    Egger D; Geuenich S; Denzlinger C; Schmitt E; Mailhammer R; Ehrenreich
       H; Dormer P; Hultner L; GSF-Institute for Experimental Hematology,
       Munich, Germany.
 SO    J Immunol. 1995 Feb 15;154(4):1830-7. Unique Identifier : AIDSLINE
       MED/95138527
 AB    It has previously been shown that mouse bone marrow-derived mast cells
       (BMMC) synthesize and secrete endothelin-1 (ET-1) and express ETA-type
       endothelin receptors (ETA-R). The study presented here was designed to
       elucidate the influence of different cytokine conditions for cellular
       differentiation and maturation on the ability of primary mouse BMMC to
       respond to exogenous ET-1. BMMC were grown for 2 wk in IL-3 alone and
       then cultured for 2 to 3 wk with kit ligand (KL) and/or IL-3 in the
       presence or absence of IL-4. ET-1 induced a very rapid (< or = 1 min)
       and dose-dependent release of histamine and serotonin from BMMC cultured
       in the presence of both IL-3 and IL-4. The effect of ET-1 was
       quantitatively comparable with IgE/Ag-induced mediator release and
       comprised up to 20% and 16% of total cellular histamine and serotonin,
       respectively. In BMMC grown with KL or KL plus IL-3, a substantial
       effect of ET-1 on amine release was only observed when IL-4 had been
       included in the culture medium. These IL-4 effects could not be observed
       if BMMC grown in IL-3 and/or KL were preincubated for 1 or 24 h with
       IL-4 before activation with ET-1, suggesting that a differentiation
       process rather than a functional priming effect had been initiated by
       IL-4. In BMMC, the histamine and serotonin release induced by ET-1
       (10(-6) M) was inhibited by an ETA-R-specific antagonist (cyclic
       [D-Asp-Pro-D-Val-Leu-D-Trp]) in a dose-dependent manner, with complete
       inhibition at an antagonist concentration of 10(-8) M. ET-1 stimulated
       leukotriene C4 biosynthesis up to 4.5-fold in BMMC cultured in the
       presence of IL-4. No such ET-1 effect was observed in BMMC cultured in
       media containing IL-3, KL, or a combination of both cytokines.
       Peritoneal cells (containing 2 to 3% serosal mast cells) obtained from
       BALB/c mice released 87 +/- 2% of histamine within 1 min after challenge
       with ET-1. Our results demonstrate that ET-1 can directly act as a
       histamine and serotonin secretagogue and as a stimulator of leukotriene
       C4 production in mast cells. IL-4 appears to be critically involved in
       the differentiation of immature mast cell precursors to an ET-1-reactive
       phenotype.(ABSTRACT TRUNCATED AT 400 WORDS)
 DE    Amino Acid Sequence  Animal  Bone Marrow/CYTOLOGY  Cell
       Differentiation/DRUG EFFECTS  Cells, Cultured  Comparative Study
       Dose-Response Relationship, Drug  Endothelins/*PHARMACOLOGY
       Hematopoietic Cell Growth Factors/PHARMACOLOGY  Histamine
       Liberation/DRUG EFFECTS  Interleukin-3/PHARMACOLOGY
       Interleukin-4/*PHARMACOLOGY  Leukotriene C4/BIOSYNTHESIS  Mast
       Cells/*DRUG EFFECTS/SECRETION  Mice  Mice, Inbred BALB C  Molecular
       Sequence Data  Organ Specificity  Peritoneal Cavity/CYTOLOGY  Receptors,
       Endothelin/ANTAGONISTS & INHIB/PHYSIOLOGY  Recombinant
       Proteins/PHARMACOLOGY  Serotonin/SECRETION  Support, Non-U.S. Gov't  Th2
       Cells/IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).