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Research Article| Volume 36, ISSUE 1, P57-61, April 1989

Radioimmunoassay of LTB4 in plasma from different species: A cautionary note

DOI:https://doi.org/10.1016/0952-3278(89)90163-4
Radioimmunoassay of LTB4 in plasma from different species: A cautionary note
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      Abstract

      In clinical and pre-clinical research the pharmacodynamics of selective 5-lipoxygenase and dual 5-lipoxygenase/cyclo-oxygenase inhibitors may be studied by direct RIA of plasma LTB4. Although immunoreactive LTB4 in plasma from A23187 stimulated human blood has the characteristics of authentic LTB4 our results show, particularly in mice and rats, that exposure to A23187 produces large quantities of 12-HETE. Since in different species the levels of 12-HETE increase with platelet concentration we suggest that the 12(S)-HETE is produced by platelet lipoxygenase. However, we do not rule out the possibility that a proportion of 12-HETE may exist as the (R)-stereoisomer. The latter has greater potential for interference in the direct RIA of LTB4. Biosynthesis of 12-HETE may be measured either by Math Eq abs. (8) or by RIA (9) and LTB4 by a more specific antibody described in this report. We conclude that the combined ex vivo RIA of plasma TXB2, LTB4 and 12-HETE has utility in determining the selectivity of inhibitors of archidonate metabolism and in distinguishing between selective 5-lipoxygenase inhibitors which interact directly with the enzyme and anti-oxidant or free radical scavenging types which may be less specific.
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      References

        • Forder R.A.
        • Carey F.
        Human 5-lipoxygenase: measurement by radioimmunoassay of LTB4 in calcium ionophore stimulated blood.
        Prostaglandins. 1984; 28: 666
        • Carey F.
        • Forder R.A.
        Radioimmunoassay of LTB4 and 6-trans LTB4: analytical and pharmacological characterisation of immunoreactive LTB4 in ionophore stimulated human blood.
        Prostaglandins Leukotrienes & Medicine. 1986; 22: 57-70
        • Carey F.
        • Forder R.A.
        • French P.
        • Haworth D.
        Differential stimulation of eicosanoid biosynthesis in human blood.
        in: II World Conference on Inflammation, Monte Carlo1986: A. 196
        • Gresele P.
        • Arnout J.
        • Coene M.C.
        • Deckmyn H.
        • Vermylen J.
        Leukotriene B4 production by stimulated whole blood: comparative studies with isolated polymorphonuclear cells.
        Biochem. Biophys. Res. Commun. 1986; 137: 334-342
        • Sweeney F.J.
        • Eskra J.D.
        • Carty T.J.
        Development of a system for evaluating 5-lipoxygense inhibitors using human whole blood.
        Prostaglandins Leukotrienes & Medicine. 1987; 28: 73-93
        • Greaves M.
        • Barr R.
        • Camp R.
        Leukotriene B4-like immunoreactivity and skin disease.
        Lancet. 1984; ii: 160
        • Carey F.
        • Forder R.A.
        • Haworth D.
        Assessment of the bioavailability and selectivity of inhibitors of arachidonic acid metabolism in whole blood.
        Brit. J. Pharmacol. 1987; 91: 404
        • Carey F.
        • Forder R.A.
        • Haworth D.
        • Woollard P.M.
        Identification and characterisation of 12-HETE biosynthesis in whole blood: implications for immunoassay of LTB4.
        Biochem. Soc. Trans. 1987; 15: 430
        • Carey F.
        • Haworth D.
        • Edmonds A.E.
        • Forder R.A.
        A simple procedure for measuring the pharmacodynamics and analgesic potential of lipoxygenase inhibitors.
        J. Pharmacol. Methods. 1987; (submitted)
        • Young R.N.
        • Zamboni R.
        • Rokach J.
        Studies on the conjugation of leukotriene B4 with proteins for development of a radioimmunoassay for leukotriene B4.
        Prostaglandins. 1983; 26: 605-613
        • McMillan R.M.
        • Millest A.J.
        • Proudman K.E.
        • Taylor K.B.
        Evaluation of lipoxygenase inhibitors ex vivo.
        Brit. J. Pharmacol. 1986; 87: 53
        • Haworth D.
        • Carey F.
        Identification of immunoreactive LTB4 in the yeast-inflamed rat paws.
        in: Higgs G.A. Williams T. Inflammatory Mediators. MacMillan Press, Basingstoke, Hants1985: 37-45
        • Simmons P.M.
        • Salmon J.A.
        • Moncada S.
        The release of leukotriene B4 during experimental inflammation.
        Biochem. Pharmacol. 1983; 32: 1353-1359
        • Foster S.J.
        • McCormick M.E.
        • Howarth A.
        • Aked D.
        Leukocyte recruitment in the subcutaneous sponge implant model of acute inflammation in the rat is not mediated by leukotriene B4.
        Biochem. Pharmacol. 1986; 35: 1709-1917
        • Ford-Hutchinson A.W.
        • Brunet G.
        • Sanard P.
        • Charleson S.
        Leukotriene B4, polymorphonuclear leukocytes and inflammatory exudates in the rat.
        Prostaglandins. 1984; 28: 13-27
        • Woollard P.M.
        Stereochemical difference between 12-hydroxy-5,8,10,14-eicosatetraenoic acid in platelets and psoriatic lesions.
        Biochem. Biophys. Res. Commun. 1986; 136: 169-176
        • Woollard P.M.
        • Carey F.
        • Forder R.A.
        12(R) HETE: a metabolite of arachidonic acid in psoriasis.
        1987 (submitted)
        • Hamberg M.
        • Samuelsson B.
        Prostaglandin endoperoxides: novel transformations of arachidonic acid in human platelets.
        in: Proc. Natl. Acad. Sci. USA. 71. 1974: 3400-3404
        • Sanderson J.H.
        • Phillips C.E.
        An atlas of laboratory animal haematology.
        Clarendon Press, Oxford1981
        • Carey F.
        • Forder R.A.
        • French P.
        • Haworth D.
        Effect of pro-inflammatory stimuli on eicosanoid biosynthesis in human blood.
        Brit. J. Pharmacol. 1986; 88: 245

      Article info

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      DOI: https://doi.org/10.1016/0952-3278(89)90163-4

      Copyright

      © 1989 Published by Elsevier Inc.

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