Lysophosphatidylserine as histamine releaser in mice and rats

Abstract

Lysophosphatidylserine is a specific inducer of histamine release in isolated mast cells. To determine whether a similar effect is manifest in vivo, the phospholipid was injected (1-5 mg/kg i.v.) into mice and rats. A dose-dependent rise in blood histamine was observed in both animals. The several-fold increase in blood histamine occurred in the first minutes and was followed by a slower decline toward normal values. A second dose of lysophosphatidylserine was without effect. Systemic manifestations (depression, hypothermia, hypotension) were associated with the increased blood histamine level. When the tissue histamine stores accessible to lysophosphatidylserine were previously decreased by repeated phospholipid injections, no systemic symptoms occurred. Mobilization of carbohydrate reserves was also manifest during the action of lysophosphatidylserine. Prior treatment with compound 48/80 induced sustained refractoriness to lysophosphatidylserine. Structure-activity relationship demonstrated that the property to induce histamine release was linked to the structure of serine head group. Thus, other natural phospholipids or lysophospholipids were inactive. It is concluded that in analogy with the effect seen in vitro lysophosphatidylserine produces in vivo release of mast cell histamine.

Local effects of lysophosphatidylserine in rats

“…When needed, the dispersion was clarified by a brief sonication (three bursts of 1 min ea6h) at 0~ All other reagents were of analytical grade (see Ref. [2]). …”

“…Lysophosphatidylserine (1-acyl-sn-glycero-3-phosphoserine) is a derivative of phosphatidylserine producing a stimulation of mast cells in vitro and in vivo [1,2]. Because of selectivity among natural phospholipids, this compound deserves consideration as a possible mast cell modulator in allergic and inflammatory conditions.…”

An Alternative Splicing Form of Phosphatidylserine-specific Phospholipase A1 That Exhibits Lysophosphatidylserine-specific Lysophospholipase Activity in Humans

“…For example, lyso-PS is demonstrated to interact with local mast cells (17), producing specific and stereoselective activation (18). It also induces transient increases in cytosolic free Ca 2ϩ ([Ca 2ϩ ] i ) in ovarian and breast cancer cells (19) and lyso-PS; 2-acyl-1-lyso-PS with unsaturated fatty acids especially inhibits mitogen-induced T cell activation (20).…”

Extracellular Phospholipase A₂ and Histamine Release from Rat Peritoneal Mast Cells

“…In addi tion to the effect of arachidonate, lysophospholipids may participate for the enhancement of antigen-in duced histamine release. There are some reports to indicate a potent membrane-perturbing activity of ly sophospholipids including lysophosphatidyl serine and lysolecithine resulted in the release of histamine or the enhancement of histamine release from mast cells [26][27][28]. The enhancement of antigen-induced histamine release in the present system may be in volved in the generation of lysophospholipid.…”