scholarly journals Group V secretory phospholipase A2 amplifies the induction of cyclooxygenase 2 and delayed prostaglandin D2 generation in mouse bone marrow culture-derived mast cells in a strain-dependent manner

2006 ◽  
Vol 1761 (12) ◽  
pp. 1489-1497 ◽  
Author(s):  
Bruno L. Diaz ◽  
Yoshiyuki Satake ◽  
Eriya Kikawada ◽  
Barbara Balestrieri ◽  
Jonathan P. Arm
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Phospholipase A2 ◽  
Bone Marrow Culture ◽  
Prostaglandin D2 ◽  
Mouse Bone Marrow ◽  
Dependent Manner ◽  
Secretory Phospholipase A2 ◽  
Group V ◽  
Strain Dependent

scholarly journals The immediate phase of c-kit ligand stimulation of mouse bone marrow-derived mast cells elicits rapid leukotriene C4 generation through posttranslational activation of cytosolic phospholipase A2 and 5-lipoxygenase.

1995 ◽  
Vol 182 (1) ◽  
pp. 197-206 ◽  
Author(s):  
M Murakami ◽  
K F Austen ◽  
J P Arm
Keyword(s):  
Bone Marrow ◽  
Arachidonic Acid ◽  
Mast Cells ◽  
Cell Membrane ◽  
Phospholipase A2 ◽  
Mouse Bone Marrow ◽  
Kit Ligand ◽  
Cytosolic Phospholipase ◽  
Delayed Phase ◽  
Stimulation Of

c-kit ligand (KL) activated mouse bone marrow-derived mast cells (BMMC) for the dose- and time-dependent release of arachidonic acid from cell membrane phospholipids, with generation of leukotriene (LT) C4 in preference to prostaglandin (PG)D2. KL at concentrations of 10 ng/ml elicited half-maximal eicosanoid generation and at concentrations of > 50 ng/ml elicited a maximal generation of approximately 15 ng LTC4 and 1 ng PGD2 per 10(6) cells, with 20% net beta-hexosaminidase release 10 min after stimulation. Of the other cytokines tested, none, either alone or in combination with KL, elicited or modulated the immediate phase of mediator release by BMMC, indicating strict specificity for KL. Activation of BMMC in response to KL was accompanied by transient phosphorylation of cytosolic phospholipase A2 and reversible translocation of 5-lipoxygenase to a cell membrane fraction 2-5 min after stimulation, when the rate of arachidonic acid release and LTC4 production were maximal. BMMC continuously exposed to KL in the presence of IL-10 and IL-1 beta generated LTC4 in marked preference to PGD2 over the first 10 min followed by delayed generation of PGD2 with no LTC4 over several hours. Pharmacologic studies revealed that PGD2 generation in the immediate phase depended on prostaglandin endoperoxide synthase (PGHS)-1 and in the delayed phase on PGHS-2. Thus, KL provided a nonallergic stimulus for biphasic eicosanoid generation by mast cells. The immediate phase is dominated by LTC4 generation with kinetics and postreceptor biosynthetic events similar to those observed after cell activation through the high affinity IgE receptor, whereas the delayed phase of slow and selective PGD2 production is mediated by induction of PGHS-2.

Cytosolic phospholipase A2 is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells

1999 ◽  
Vol 59 (1-6) ◽  
pp. 39
Author(s):  
Bruno L. Diaz ◽  
Hiroshi Fujishima ◽  
RenéO. Sanchez Mejia ◽  
Adam Sapirstein ◽  
Joseph V. Bonventre ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Phospholipase A2 ◽  
Cytosolic Phospholipase A2 ◽  
Mouse Bone Marrow ◽  
Cytosolic Phospholipase

scholarly journals IgE-mediated release of leukotriene C4, chondroitin sulfate E proteoglycan, beta-hexosaminidase, and histamine from cultured bone marrow-derived mouse mast cells.

1983 ◽  
Vol 157 (1) ◽  
pp. 189-201 ◽  
Author(s):  
E Razin ◽  
J M Mencia-Huerta ◽  
R L Stevens ◽  
R A Lewis ◽  
F T Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Chondroitin Sulfate ◽  
Specific Antigen ◽  
Antigen Challenge ◽  
Prostaglandin D2 ◽  
Mouse Bone Marrow ◽  
Leukotriene C4 ◽  
Chondroitin Sulfate E

Mouse bone marrow-derived mast cells differentiated in vitro and sensitized with monoclonal IgE respond to antigen-initiated activation with the release of histamine, beta-hexosaminidase, chondroitin sulfate E proteoglycan, and leukotriene C4 (LTC4). The chondroitin sulfate E nature of the glycosaminoglycan side chain was established by demonstrating that the chondroitinase ABC disaccharide digestion products were composed of equal quantities of 4-sulfated and 4,6-disulfated N-acetyl-galactosamine. The single immunoreactive sulfidopeptide leukotriene, released and quantitated with a class-specific antibody, was identified as LTC4 by its retention time on reverse-phase high-performance liquid chromatography and by its specific spasmogenic activity on the guinea pig ileum. The release of the preformed mediators, as well as of LTC4, was related in a dose-response fashion to the concentration of monoclonal IgE used during the sensitization step and to the concentration of specific antigen used to initiate the activation-secretion response. The optimal concentrations of IgE for sensitization and of antigen for challenge were the same for the release of preformed mediators and of LTC4. In addition, the time courses of their release were superimposable, with a plateau at 5 min after antigen challenge. The release of three preformed mediators and of LTC4 after fixation of IgE, washing of the sensitized cells, and antigen challenge unequivocally indicates a bone marrow-derived mast cell origin for these products. Linear regression analyses of the net percent release of beta-hexosaminidase to histamine and of 35S-chondroitin sulfate E to beta-hexosaminidase yielded straight lines that intersected at the origin, which indicates that the three preformed mediators are localized in the secretory granules of the bone marrow-derived mast cells. The concomitant generation of 23 ng of LTC4/10(6) sensitized bone marrow-derived mast cells represents the first example of IgE-dependent release of substantial amounts of LTC4, a component of slow reacting substance of anaphylaxis, from a mast cell population of greater than 95% purity. The IgE-dependent generation of LTC4, rather than prostaglandin D2, by the chondroitin sulfate E proteoglycan-containing bone marrow-derived mast cells contrasts with the predominant generation of prostaglandin D2 by heparin proteoglycan-containing mast cells. These differences together support the existence of two phenotypically different mast cell subclasses.

scholarly journals Role of cytosolic phospholipase A2 in the production of lipid mediators and histamine release in mouse bone-marrow-derived mast cells

2000 ◽  
Vol 352 (2) ◽  
pp. 311-317 ◽  
Author(s):  
Noriaki NAKATANI ◽  
Naonori UOZUMI ◽  
Kazuhiko KUME ◽  
Makoto MURAKAMI ◽  
Ichiro KUDO ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Phospholipase A2 ◽  
Lipid Mediators ◽  
Cytosolic Phospholipase A2 ◽  
Prostaglandin D2 ◽  
Wild Type ◽  
Cytosolic Phospholipase

Cytosolic phospholipase A2 (cPLA2) plays a critical role in mast-cell-related allergic responses [Uozumi, Kume, Nagase, Nakatani, Ishii, Tashiro, Komagata, Maki, Ikuta, Ouchi et al. (1997) Nature (London) 390, 618–622]. Bone-marrow-derived mast cells from mice lacking cPLA2 (cPLA-/- mice) were used in order to better define the role of cPLA2 in the maturation and degranulation of such cells. Cross-linking of high-affinity receptors for IgE (FcεRI) on cells from cPLA-/-mice led to the release of negligible amounts of arachidonic acid or its metabolites, the cysteinyl leukotrienes and prostaglandin D2, indicating an essential role for cPLA2 in the production of these allergic and pro-inflammatory lipid mediators. In addition, the histamine content of the mast cells and its release from the cells were reduced to 60%. While these results are in agreement with a reduced anaphylactic phenotype of cPLA-/- mice, the ratios of release of histamine and β-hexosaminidase were, paradoxically, significantly higher for cells from cPLA-/- mice than for those from wild-type mice. Consistently, IgE-induced calcium influx in mast cells was greater and more prolonged in cells from cPLA-/- mice than in those from wild-type mice. Thus the loss of cPLA2 not only diminishes the release of lipid mediators, but also alters degranulation. While the overall effect is still a decrease in the release of mast cell mediators, explaining the in vivo findings, the present study proposes a novel link between cPLA2 and the degranulation machinery.

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