Limit of detection: 80% B/B₀: 13 pg/ml · Sensitivity: 50% B/B₀: 50 pg/ml · Leukotriene B₄ (LTB₄) is synthesized from arachidonic acid by the combined action of 5-lipoxygenase and LTA₄ hydrolase.¹ LTB₄ has long been recognized as a potent mediator of inflammation. It stimulates a number of leukocyte functions, including aggregation, stimulation of ion fluxes, enhancement of lysosomal enzyme release, superoxide anion production, chemotaxis, and chemokinesis.^2,3 In subnanomolar ranges (3.9 x 10⁻¹⁰ M), LTB₄ causes chemotaxis and chemokinesis in human PMNLs.² At higher concentrations, (1.0 x 10⁻⁷ M), LTB₄ leads to neutrophil aggregation and degranulation as well as superoxide anion production.^2,4 Plasma levels of LTB₄ increase from <100 pg/ml to >100 ng/ml following leukocyte stimulation.^5,6,7 LTB₄ is metabolized in leukocytes and hepatocytes to less active 20-hydroxy and 20-carboxy LTB₄ by NADPH-dependent cytochrome P450 enzymes followed by β-oxidation at the ω-end to ω-carboxy dinor LTB₄ and ω-carboxy tetranor LTB₃.^3,8,9,10 LTB₄ is not excreted in the urine.¹¹

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2 Ford-Hutchinson, A.W. Leukotriene B₄ in inflammation. Crit Rev Immunol 10 1-12 (1990).

3 Mayatepek, E., and Hoffmann, G.F. Leukotrienes: Biosynthesis, metabolism, and pathophysiologic significance. Pediatr Res 37 1-9 (1995).

4 Fretland, D.J., Widomski, D.L., Anglin, C.P., et al. 6-trans-Leukotriene B₄ is a neutrophil chemotoxin in the guinea pig dermis. J Leukoc Biol 49 283-288 (1991).

5 Surette, M.E., Odeimat, A., Palmantier, R., et al. Reverse-phase high-performance liquid chromatography analysis of arachidonic acid metabolites in plasma after stimulation of whole blood ex vivo. Anal Biochem 216 392-400 (1994).

6 Shindo, K., Fukumura, M., and Miyakawa, K. Leukotriene B₄ levels in the arterial blood of asthmatic patients and the effects of prednisolone. Eur Respir J 8 605-610 (1995).

7 Doyle, M.J., Eichhold, T.H., Hynd, B.A., et al. Determination of leukotriene B₄ in human plasma by gas chromatography using a mass selective detector and a stable isotope labelled internal standard. Effect of NE-11740 on arachidonic acid metabolism. J Pharm Biomed Anal 8 137-142 (1990).

8 Hammarström, S., Örning, L., and Bernström, K. Metabolism of leukotrienes. Mol Cell Biochem 69 7-16 (1985).

9 Harper, T.W., Garrity, M.J., and Murphy, R.C. Metabolism of leukotriene B₄ in isolated rat hepatocytes. Identification of a novel 18-carboxy-19,20-dinor leukotriene B₄ metabolite. J Biol Chem 261 5414-5418 (1986).

10 Hansson, G., Lindgren JÅ, Dahlén, S., et al. Identification and biological activity of novel w-oxidized metabolites of leukotriene B₄ from human leukocytes. FEBS Lett 130 107-112 (1981).

11 Serafin, W.E., Oates, J.A., and Hubbard, W.C. Metabolism of leukotriene B₄ in the monkey. Identification of the principal nonvolatile metabolite in the urine.. Prostaglandins 27 899-911 (1984).

Harper, T.W., Garrity, M.J., and Murphy, R.C. Metabolism of leukotriene B₄ in isolated rat hepatocytes. Identification of a novel 18-carboxy-19,20-dinor leukotriene B₄ metabolite. J Biol Chem 261 5414-5418 (1986).

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Doyle, M.J., Eichhold, T.H., Hynd, B.A., et al. Determination of leukotriene B₄ in human plasma by gas chromatography using a mass selective detector and a stable isotope labelled internal standard. Effect of NE-11740 on arachidonic acid metabolism. J Pharm Biomed Anal 8 137-142 (1990).

Fretland, D.J., Widomski, D.L., Anglin, C.P., et al. 6-trans-Leukotriene B₄ is a neutrophil chemotoxin in the guinea pig dermis. J Leukoc Biol 49 283-288 (1991).

Ford-Hutchinson, A.W. Leukotriene B₄ in inflammation. Crit Rev Immunol 10 1-12 (1990).

Hansson, G., Lindgren JÅ, Dahlén, S., et al. Identification and biological activity of novel w-oxidized metabolites of leukotriene B₄ from human leukocytes. FEBS Lett 130 107-112 (1981).

Hammarström, S., Örning, L., and Bernström, K. Metabolism of leukotrienes. Mol Cell Biochem 69 7-16 (1985).

Cott, G.R., Westcott, J.Y., and Voelkel, N.F. Prostaglandin and leukotriene production by alveolar type II cells in vitro. Am J Physiol 258 L179-L187 (1990).

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Shindo, K., Fukumura, M., and Miyakawa, K. Leukotriene B₄ levels in the arterial blood of asthmatic patients and the effects of prednisolone. Eur Respir J 8 605-610 (1995).

Serafin, W.E., Oates, J.A., and Hubbard, W.C. Metabolism of leukotriene B₄ in the monkey. Identification of the principal nonvolatile metabolite in the urine.. Prostaglandins 27 899-911 (1984).

Surette, M.E., Odeimat, A., Palmantier, R., et al. Reverse-phase high-performance liquid chromatography analysis of arachidonic acid metabolites in plasma after stimulation of whole blood ex vivo. Anal Biochem 216 392-400 (1994).

Samuelsson, B., and Funk, C.D. Enzymes involved in the biosynthesis of leukotriene B₄. J Biol Chem 264 19469-19472 (1989).

Pradelles, P., Grassi, J., and Maclouf, J.A. Enzyme immunoassays of eicosanoids using acetylcholinesterase as label: An alternative to radioimmunoassay. Anal Chem 57 1170-1173 (1985).

Mayatepek, E., and Hoffmann, G.F. Leukotrienes: Biosynthesis, metabolism, and pathophysiologic significance. Pediatr Res 37 1-9 (1995).

Silbaugh, S.A., Stengel, P.W., Cockerham, S.L., et al. Pulmonary actions of LY255283, a leukotriene B₄ receptor antagonist. Eur J Pharmacol 223 57-64 (1992).

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Coffey, M.J., Wilcoxen, S.E., Phare, S.M., et al. Reduced 5-lipoxygenase metabolism of arachidonic acid in macrophages from 1,25-dihydroxyvitamin D₃-deficient rats. Prostaglandins 48 313-329 (1994).

Thivierge, M., and Rola-Pleszczynski, M. Involvement of both cyclooxygenase and lipoxygenase pathways in platelet-activating factor-induced interleukin-6 production by alveolar macrophages. Ann N Y Acad Sci 725 213-222 (1994).

Marshall, L.A., Bolognese, B., Winkler, J.D., et al. Depletion of human monocyte 85-kDa phospholipase A₂ does not alter leukotriene formation. J Biol Chem 272 759-765 (1997).

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Bozza, P.T., Payne, J.L., Morham, S.G., et al. Leukocyte lipid body formation and eicosanoid generation: Cyclooxygenase-independent inhibition by aspirin. Proc Natl Acad Sci USA 93 11091-11096 (1996).

Anderson, K.M., Roshak, A., Winkler, J.D., et al. Cytosolic 85-kDa phospholipase A₂-mediated release of arachidonic acid is critical for proliferation of vascular smooth muscle cells. J Biol Chem 272 30504-30511 (1997).

Celardo, A., Dell'Elba, G., Manarini, S., et al. Kinetics of endogenous leukotriene B₄ and E₄ production following injection of the chemotactic peptide FMLP in the rabbit. Prostaglandins 54 699-711 (1997).

Blair, R.M., Saatman, R., Liou, S.S., et al. Roles of leukotrienes in bovine corpus luteum regression: An in vivo microdialysis study. Proc Soc Exp Biol Med 216 72-80 (1997).

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Nakao, A., Watanabe, T., Ohishi, N., et al. Ubiquitous localization of leukotriene A₄ hydrolase in the rat nephron. Kidney Int 55 100-108 (1999).

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