Platelet-activating factor (PAF-acether) induced leukotriene C4 formation and luminol dependent chemiluminescence by human eosinophils.
Human eosinophils are capable of synthesizing almost exclusively the strongly spasmogenic compound LTC4 when stimulated with either the calcium ionophore A 23187 or opsonized zymosan (OZ). Although PAF-acether in concentrations ranging from 10 nM to 1 microM is hardly capable of inducing significant LTC4 synthesis itself, it significantly enhances the OZ-induced LTC4 formation at a concentration of 1 microM. However, at a concentration of 10 microM, PAF-acether itself is capable of inducing LTC4 formation comparable with that induced by OZ. PAF-acether, at a concentration of 10 microM (and not at a concentration of 1 microM) is also capable of inducing a luminol dependent chemiluminescent response by eosinophils. The PAF-acether antagonist BN 52021 at a concentration of 0.1 mM not only partially inhibited the PAF-acether induced LTC4 formation but also the OZ induced LTC4 formation. Since an equal inhibition is found the inhibitory mode of action of BN 52021 is most likely directed towards a common pathway. Taken together, these results suggest that eosinophils may be triggered by high locally reached concentrations of PAF-acether to release inflammatory and bronchoconstrictive mediators. This may be of importance for the pathogenesis of the allergen induced late phase asthmatic reaction.
D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008165:Luminol / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000502:physiology*; D011724:Pyridazines / Q000502:physiology*; D013189:SRS-A / Q000096:biosynthesis*; D015054:Zymosan / Q000494:pharmacology
D010972:Platelet Activating Factor; D011724:Pyridazines; D013189:SRS-A; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008165:Luminol; D015054:Zymosan