Effects of L-leucine methyl ester (Leu-OMe) on mouse peritoneal mast cells: characterization of histamine release versus cytotoxicity.
L-Leucine methyl ester (Leu-OMe), a lysosomotropic compound, has been found to eliminate several lysosome-rich cellular subtypes and all natural killer cell function from peripheral blood mononuclear cells. In this report, the effect of Leu-OMe on mouse peritoneal mast cells is described. The L-Leu-OMe induced the release of histamine from mouse peritoneal mast cells in a dose-dependent manner (0.25 to 3 mM), while its D-stereoisomer had no effect. L-Leu-OMe displayed also a potent histamine release effect on purified mast cells, indicating a direct effect on mast cells. The monitoring of radioactive chromium release versus histamine release showed that both processes may be unrelated for Leu-OMe concentrations inferior to 1.5 mM. At higher doses, L-Leu-OMe, but not its D-stereoisomer, exerted a potent cytotoxic effect on mast cells. The secretory effect of Leu-OMe was temperature- and energy-dependent. Experiments performed in the absence of extracellular calcium and magnesium demonstrated that these divalent cations were not necessary for the Leu-OMe-induced histamine release, and their deprivation even involved a higher histamine release. The secretory characteristics of the Leu-OMe-induced histamine release appeared to be different from those of the IgE-induced ones. These results support the conclusion that exposure of mouse peritoneal mast cells to high doses of L-Leu-OMe results in killing of these cells, that are new targets of this lysosomotropic agent.
Unité d'Immuno-Allergie, Institut Pasteur, Paris, France.
C
C
Oskeritzian
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A
Prouvost-Danon
B
B
David
D000818:Animals; D000906:Antibodies; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release; D007073:Immunoglobulin E; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D010537:Peritoneum; D013696:Temperature
D000906:Antibodies; C030365:leucine methyl ester; D007073:Immunoglobulin E; D007930:Leucine