Calcium-ionophore-induced formation of platelet-activating factor and leukotrienes by horse eosinophils: a comparative study.
Horse eosinophils preincubated with 3H-labelled acetate and stimulated with the Ca2+ ionophores ionomycin or A23187 form a radioactive compound, which we have shown to be 1-O-alkyl-2-[3H]acetyl-sn-glycero-3-phosphocholine (platelet-activating factor). We could detect no 1-O-acyl-2-[3H]acetyl-glycero-3-phosphocholine in the radioactive fraction. The formation of platelet-activating factor was strongly correlated to the generation of leukotriene C4, the main arachidonate metabolite in horse eosinophils, suggesting that platelet-activating factor and leukotriene C4 have a common precursor pool (1-O-alkyl-2-arachidonyl-glycero-3-phosphocholine) and a common regulation of synthesis. Even though both ionomycin and A23187 are described as Ca2+ ionophores, they have a series of significantly different effects on the eosinophils with respect to formation of platelet-activating factor and leukotriene C4. While A23187 induces an asymptotic maximum of mediator formation at concentrations higher than 20 microM, ionomycin expressed a narrow optimum at 2 microM. The effects of exogenous pH on the release of mediators also differ strongly between the two ionophores: for A23187 the effects are the same for both mediators but when ionomycin is used as stimulant, generation of platelet-activating factor and leukotriene C4 are affected differently.
Asmis
R
R
Department of Biochemistry, University of Fribourg, Switzerland.
Jörg
A
A
D000818:Animals; D002021:Buffers; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D006736:Horses; D006863:Hydrogen-Ion Concentration; D015759:Ionomycin / Q000494:pharmacology*; D009550:Nigericin / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D011817:Rabbits; D013189:SRS-A / Q000096:biosynthesis*
D002021:Buffers; D010972:Platelet Activating Factor; D013189:SRS-A; D000001:Calcimycin; D015759:Ionomycin; D009550:Nigericin; D002118:Calcium