Complement receptor enhancement and chemotaxis of human neutrophils and eosinophils by leukotrienes and other lipoxygenase products.
The lipoxygenase products of arachidonic acid, 5-HPETE, 5-HETE, LTB4, LTC4 and LTD4, were examined for their capacity to enhance the expression of complement (C3b) receptors and to evoke chemotaxis of human neutrophils and eosinophils. With the exception of LTD4 all gave enhancement of C3b receptors. LTB4 and LTC4 enhanced over the concentration range 10(-7) to 10(-11) moles/l, and 5-HETE and 5-HPETE from 5 X 10(-6) to 5 X 10(-10) moles/l. The rank order of activity, as assessed by the magnitude of enhancement, was LTB4 (concentration for maximal effect = 10(-7) moles/l) greater than 5-HETE (5 X 10(-7)) greater than 5-HPETE (5 X 10(-6)) greater than LTC4 (10(-9)). High dose inhibition was observed with LTC4 and 5-HETE. Chemotaxis experiments performed in parallel over the same concentration ranges indicated that neither neutrophils nor eosinophils migrated towards LTC4 or LTD4. However, LTB4 evoked chemotaxis with a linear dose response from 10(-9) to 10(-7) moles/l and 5-HPETE and 5-HETE from 5 X 10(-8) to 5 X 10(-6) moles/l. At 10(-7) moles/l LTB4 was approximately 6 and 8 X more potent in chemotaxis than 5-HPETE and 5-HETE respectively. In general, complement receptor enhancement and chemotaxis of eosinophils were similar to that observed with neutrophils and did not vary with the patient source.
D001091:Arachidonate Lipoxygenases; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004804:Eosinophils / Q000187:drug effects; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids; D066298:In Vitro Techniques; D007975:Leukotriene B4; D015289:Leukotrienes; D008054:Lipid Peroxides; D008084:Lipoxygenase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D010545:Peroxides / Q000494:pharmacology; D011951:Receptors, Complement / Q000187:drug effects*; D013189:SRS-A / Q000494:pharmacology*
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D010545:Peroxides; D011951:Receptors, Complement; D013189:SRS-A; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase