Leukotrienes (LTC4, LTD4) confer glass non-adherence on leukocytes of asthmatic individuals. Dependency on cyclooxygenase products and calcium ion.
It has been suggested that cysteinyl-containing leukotrienes (LT) are important mediators in bronchial asthma. Since leukotrienes have been shown to mediate the leukocyte adherence inhibition (LAI) phenomenon observed in cancer-bearing host we have devised a modified LAI assay which determines the acquisition of non-adherence properties of leukocytes following a challenge with pure synthetic LT. Our results demonstrate that peripheral blood leukocytes of asthmatic individuals acquire non-adherence properties when challenged with pure synthetic leukotriene C4 and D4, a property not shared by peripheral blood leukocytes of control healthy individuals. Furthermore, we demonstrate that LT activity as manifested by the LAI assay is dependent on cyclooxygenase products, since 2 X 10(-6) M Indomethacin abrogated the LT-induced LAI and is restored by the addition of 2 X 10(-6) M prostaglandin E2 which is also synergistic to LT activity. Our results further suggest the possibility that leukotriene activity is dependent on calcium ions since it was negated by known calcium antagonists. It is thus suggested that the LT-induced LAI may serve as a tool for the study of the interrelationship between the metabolic pathways of arachidonic acid and calcium ion homeostasis.
D001249:Asthma / Q000276:immunology*; D002118:Calcium / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects*; D002648:Child; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D005898:Glass; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D007957:Leukocyte Adherence Inhibition Test; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D013189:SRS-A; D014268:Trifluoperazine; D007811:Lanthanum; D008012:Lidocaine; D011451:Prostaglandin-Endoperoxide Synthases; D009543:Nifedipine; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin