Enhancement of neutrophil- and eosinophil-mediated complement-dependent killing of schistosomula of Schistosoma mansoni in vitro by leukotriene B4.
We have studied the ability of leukotrienes and other lipoxygenase products of arachidonic acid (AA) to influence complement-dependent killing of schistosomula of Schistosoma mansoni in vitro by human neutrophils or eosinophils. These lipid mediators, which included LTB4, LTC4, LTD4, 5-HETE and 5-HPETE, had no apparent effect, by themselves, on schistosomular motility or viability. However, in the presence of granulocytes and fresh serum (as a source of complement) LTB4 (but not LTC4, LTD4, 5-HETE or 5-HPETE) enhanced neutrophil- and (to a much lesser extent) eosinophil mediated, complement-dependent killing. These effects varied with the concentration of LTB4, the dilution of complement and time of incubation. The percentage of LTB4-induced enhancement obtained with neutrophils was greater than that observed with eosinophils (although the latter were obtained from patients with helminthic parasitic disease). The synthetic bacterial analogue f-Met-Leu-Phe, also known to amplify complement associated granulocyte events, was comparable to LTB4 in its ability to enhance neutrophil- and eosinophil-mediated, complement-dependent killing of schistosomula. These results indicate that LTB4, which is released in mast cell associated reactions and promotes cell locomotion and enhancement of complement receptors in vitro, increases neutrophil- and eosinophil-mediated, complement-dependent damage of schistosomula, possibly through enhancement of C3b receptors and that this may be an important amplification mechanism in IgE related immunity to migrating helminthic larvae.
D001095:Arachidonic Acids / Q000494:pharmacology; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4 / Q000494:pharmacology*; D015289:Leukotrienes; D009504:Neutrophils / Q000276:immunology*; D013189:SRS-A / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000276:immunology*
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D013189:SRS-A; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C025348:arachidonic acid 5-hydroperoxide; D003165:Complement System Proteins