Phosphatidylserine-specific Phospholipase A1Stimulates Histamine Release from Rat Peritoneal Mast Cells through Production of 2-Acyl-1-lysophosphatidylserine (original) (raw)
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Biochemical Journal, 2000
Cytosolic phospholipase A # (cPLA # ) plays a critical role in mastcell-related allergic responses Nature (London) 390, 618-622]. Bone-marrow-derived mast cells from mice lacking cPLA # (cPLA V / V # mice) were used in order to better define the role of cPLA # in the maturation and degranulation of such cells. Cross-linking of high-affinity receptors for IgE (FcεRI) on cells from cPLA V / V # mice led to the release of negligible amounts of arachidonic acid or its metabolites, the cysteinyl leukotrienes and prostaglandin D # , indicating an essential role for cPLA # 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
Interaction of phosphatidylserine with mast cells
Proceedings of the National Academy of Sciences, 1978
Phosphatidylserine (PtdSer) potentiates histamine secretion from mast cells exposed to concanavalin A and Ca2+. In order to identify the form of PtdSer that is responsible for its effect on mast cell secretion, PtdSer containing a tritium-labeled serine moiety (3H-PtdSer) was synthesized from egg yolk phosphatidylcholine. The critical micele concentration (CMC) of 3H-PtdSer and the binding isotherm for 3H-PtdSer interaction with mast cells were determined. The midpoints of the binding isotherm and the dose-response curve for potentiation of secretion coincide and are 2 orders of magnitude greater than the CMC. The shape of the binding curve is explicable either in terms of simple binding of preformed PtdSer micelles or of cooperative binding of monomeric PtdSer in which the number of molecules cooperatively associating with a mast cell binding site is equal to the number of monomers in a PtdSer micelle. In either case, at equilibrium, PtdSer micelles are bound to the mast cells. The number of PtdSer molecules bound to a single mast cell at equilibrium was estimated to be 3.7 X l0s.
European Journal of Biochemistry
Group I1 phospholipase A, was detected in appreciable amounts in rat peritoneal mast cells. The effect of several inhibitors specific to 14-kDa group-I1 phospholipase A,, including two proteinaceous inhibitors and a product of microorganisms with a low molecular mass, on mast-cell activation was examined. When rat peritoneal mast cells werc sensitized with IgE and then challenged with antigen, the specific phospholipase-A2 inhibitors suppressed histamine release in a concentration-dependent manner. By contrast, these inhbitors showed no effect on prostaglandin generation under the same conditions. Histamine release from rat peritoneal mast cells subjected to non-immunochemical stimuli, such as concanavalin A, the Ca2+ ionophorc A23187, compound 48/80 and substance P was also suppressed. When rat peritoneal mast cells were treated with 14-kDa-group-II-phospholipase-A,specific inhibitors, washed and stimulated, histamine release was not affected appreciably. Similar suppressive effects of the inhibitors on histamine release were observed with mouse cultured bonemarrow-derived mast cells. When bone-marrow-derived mast cells were activated, they secreted both a soluble and an ecto-enzyme form of 1CkDa group-I1 phospholipase A2, although appearance of
Signalling mechanism in the lysophosphatidylserine-induced activation of mouse mast cells
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1990
Lysophosphatidyiserine (0.1-1 /tM) elicits histamine release in isolated mouse peritoneal mast cells. The effect becomes manifest after a lag of 30 s and reaches completion in 5 min. Maximal activity is observed when serine is in L-configuration. As shown by the activity of a lysophosphatidylserine analogue lacking the OH group in C2 position of glycerol, conversion into phosphatidylserine is not required. When 32po4-1aheled mast cells are challenged 2-5 min with lysophosphatidylserine, the labeling of phosphatidate, phosphatidylinositol and phosphatidylcholine is increased. When {3Hlarachidonate-laheled mast cells are used, lysophosphatidylserine increases the appearance of isotopic diacylglycerol and phosphatidate. Like the secretory response, these effects are independent of the presence of extracellular Ca 2+.
Different responses of rodent mast cells to lysophosphatidylserine
Inflammation Research, 1984
The lysophosphatidylserine-induced activation of mast cells has been studied in preparations obtained from different rodents. In mouse and gerbil peritoneal mast cells lysophosphatidylserine behaves as an agonist, inducing noncytotoxic histamine release at 0.2–8 μM. In rat peritoneal and pleural mast cells lysophosphatidylserine is ineffective, but the histamine-releasing activity becomes manifest upon the addition of suboptimal concentrations of other mast cell activators. The common structure-activity relationship shows the link between these effects of lysophosphatidylserine but the calcium requirement indicates differences in the mechanism of action. Histamine release in mouse mast cells is independent of external calcium. Thus, lysophosphatidylserine induces mobilization of endogenous calcium stores in these cells. By contrast, histamine release in gerbil and rat mast cells is dependent on the addition of external calcium indicating that the phospholipid promotes calcium influx. While in gerbil mast cells calcium influx is promoted by lysophosphatidylserine alone, in rat it requires the combined action of the phospholipid and other mast cell agonists. Differently from lysophosphatidylserine, compound 48/80 elicits histamine release in rat and gerbil mast cells. Mouse mast cells are unaffected. Thus, gerbil mast cells are the only preparation in which the action of these two agonists can be observed simultaneously.
Analysis of the Secretory Phospholipase A2 That Mediates Prostaglandin Production in Mast Cells
Journal of Biological Chemistry, 1997
Prostaglandin D 2 (PGD 2 ) synthesis in activated mast cells occurs in two phases, an early phase that is dependent on prostaglandin synthase 1 and a delayed phase that is dependent on activation-induced prostaglandin synthase 2 gene expression. Early phase PGD 2 synthesis in activated mast cells also requires the activity of a secretory phospholipase A 2 (PLA 2 ). It has been thought that the secretory PLA 2 expressed in mast cells is group IIa PLA 2 , encoded by the Pla2 g2a gene. However, activated bone marrow-derived mast cells prepared from Pla2 g2a ؉/؉ mice and mast cells prepared from mice with a mutation in the Pla2 g2a gene both demonstrate early phase PGD 2 synthesis. Moreover, mast cells from both murine strains secrete PLA 2 activity following activation. Northern and reverse transcriptase/polymerase chain reaction analyses demonstrate that mast cells from Pla2 g2a ؉/؉ and Pla2 g2a ؊/؊ mice do not express group IIa PLA 2 message. Instead, Northern and reverse transcriptase/polymerase chain reaction analyses demonstrate that both Pla2 g2a ؉/؉ and Pla2 g2a ؊/؊ mast cells express mRNA for group V PLA 2 , encoded by the Pla2gV gene. An antisense oligonucleotide directed against group V PLA 2 is also able to inhibit both the early phase of PGD 2 production and the secretion of PLA 2 activity by activated mast cells. Our data suggest that (i) group IIa PLA 2 does not play a significant role in murine mast cell prostaglandin synthesis, (ii) group V PLA 2 mediates early mast cell PGD 2 production and transcellular PGE 2 production in murine mast cells, and (iii) much of the data, based on studies with chemical inhibitors and antibodies, suggesting that group IIa PLA 2 is responsible for arachidonic acid mobilization needs to be reevaluated.
Lysophosphatidic acid accelerates the development of human mast cells
Blood, 2004
Mast cells (MCs) initiate immune responses from mucosal surfaces and perivascular spaces. Stem cell factor (SCF) regulates MC development and viability, but the role of innate serum factors in MC development is unexplored. Cultured cord blood-derived human MCs (hMCs) express mRNA transcripts for all 4 known receptors for lysophosphatidic acid (LPA), an abundant serum-associated lipid growth factor. In an SCF-dependent serum-free culture system, LPA (2.5-10 μM) increased the total number of hMCs by approximately 10-fold compared with cultures maintained in the absence of LPA under otherwise identical conditions. LPA was comitogenic with SCF but did not prolong MC survival. LPA-mediated proliferation was blocked by VPC-32179, a competitive antagonist of LPA1 and LPA3 receptors, and by pertussis toxin, and it was also attenuated by GW9662, a selective antagonist of peroxisome proliferator-activated receptor (PPAR)-γ. LPA accelerated the acquisition of hMC granules and increased Kit exp...