Limit of detection: 80% B/B₀: 10 pg/ml · Sensitivity: 50% B/B₀: 45 pg/ml · The leukotrienes (LTs) were discovered in 1979 as a group of acute inflammatory mediators derived from arachidonic acid in leukocytes.^1,2 Their biosynthesis was shown to proceed via the 5-lipoxygenase (5-LO) pathway. LT biosynthesis has subsequently been demonstrated in other bone marrow-derived cells expressing 5-LO including eosinophils, mast cells, and macrophages. 5-LO converts arachidonic acid into LTA₄ with 5(S)-HpETE as an intermediate. The conjugation of glutathione to LTA₄ results in the formation LTC₄. LTC₄ is rapidly metabolized to LTD₄ and LTE₄ as shown in Figure 1 (see below).³ This metabolism is essentially complete within 10 minutes in the human lung. LTC₄, LTD₄, and LTE₄ are collectively referred to as cysteinyl-leukotrienes (cys-LTs). LTC₄ and LTD₄ are potent mediators of asthma and hypersensitivity. They induce bronchoconstriction, increase microvascular permeability, and are vasoconstrictors of coronary arteries.^2,4,5 Cys-LTs can accumulate to relatively high concentrations in the effusion fluids associated with inflammation (e.g., ascities fluid, synovial fluid, pleural effusion, pericardial or cerebral aspirates). Since LT metabolism is incomplete in these circumstances, substantial amounts of LTC₄, LTD₄, and LTE₄ may be present (e.g., bronchalveolar lavage fluid from asthmatic subjects may contain 700-1,000 pg/ml of cys-LTs comprised mainly of LTC₄ and LTD₄).⁶ Cys-LTs are excreted in urine as intact LTE₄ (~9-12%) and LTE₄ metabolites. Since LTC₄ and LTD₄ and virtually absent from urine, the cys-LT measurement in urine is often best accomplished by measuring LTE₄ (LTE₄ EIA Kit, Catalog No. 520411). Cultured cells synthesizing LTC₄ will generally release it into the medium where it will accumulate without further metabolism.

1 Samuelsson, B., Dahlén, S., Lindgren JÅ, et al. Leukotrienes and lipoxins: Structures, biosynthesis, and biological effects. Science 237 1171-1176 (1987).

2 Piper, P.J. Formation and actions of leukotrienes. Physiol Rev 64 744-761 (1984).

3 Campbell, B.J., Baker, S.F., Shukla, S.D., et al. Bioconversion of leukotriene D₄ by lung dipeptidase. Biochim Biophys Acta 1042 107-112 (1990).

4 Dahlén, S., Björk, J., Hedqvist, P., et al. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: In vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci USA 78 3887-3891 (1981).

5 Westcott, J.Y., Johnston, K., Batt, R.A., et al. Measurement of peptidoleukotrienes in biological fluids. Am J Physiol 232 2640-2648 (1990).

6 Matsumoto, S., Hayashi, Y., Kinoshita, I., et al. Immunoaffinity purification of prostaglandin E₂ and leukotriene C₄ prior to radioimmunoassay: Application to human synovial fluid. Ann Clin Biochem 30(Part I) 60-68 (1993).

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).

Knight, J., Holland, J.W., Bowden, L.A., et al. Eicosanoid generating capacities of different tissues from the rainbow trout, Oncorhynchus mykiss. Lipids 30 451-458 (1995).

Maclouf, J., Grassi, J., and Pradelles, P. Development of enzyme-immunoassay techniques for the measurement of eicosanoids. 355-364 (1987).

Westcott, J.Y., Johnston, K., Batt, R.A., et al. Measurement of peptidoleukotrienes in biological fluids. Am J Physiol 232 2640-2648 (1990).

Samuelsson, B., Dahlén, S., Lindgren JÅ, et al. Leukotrienes and lipoxins: Structures, biosynthesis, and biological effects. Science 237 1171-1176 (1987).

Piper, P.J. Formation and actions of leukotrienes. Physiol Rev 64 744-761 (1984).

Pradelles, P., Antoine, C., Lellouche, J., et al. Enzyme immunoassays for leukotrienes C₄ and E₄ using acetylcholinesterase. Methods Enzymol 187 82-89 (1990).

Maclouf, J.A., and Murphy, R.C. Transcellular metabolism of neutrophil-derived leukotriene A₄ by human platelets. A potential cellular source of leukotriene C₄. J Biol Chem 263 174-181 (1988).

Wilborn, J., Bailie, M., Coffey, M., et al. Constitutive activation of 5-lipoxygenase in the lungs of patients with idiopathic pulmonary fibrosis. J Clin Invest 97 1827-1836 (1996).

Powell, W.S. Reversed-phase high-pressure liquid chromatography of arachidonic acid metabolites formed by cyclooxygenase and lipoxygenases. Anal Biochem 148 59-69 (1985).

Campbell, B.J., Baker, S.F., Shukla, S.D., et al. Bioconversion of leukotriene D₄ by lung dipeptidase. Biochim Biophys Acta 1042 107-112 (1990).

Dahlén, S., Björk, J., Hedqvist, P., et al. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: In vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci USA 78 3887-3891 (1981).

Matsumoto, S., Hayashi, Y., Kinoshita, I., et al. Immunoaffinity purification of prostaglandin E₂ and leukotriene C₄ prior to radioimmunoassay: Application to human synovial fluid. Ann Clin Biochem 30(Part I) 60-68 (1993).

Tremblay, G.M., Israel-Assayag, E., Sirois, P., et al. Murine hypersensitivity pneumonitis: Evidences for the role of eicosanoids and platelet activating factor. Immunol Invest 22 341-352 (1993).

Maxey, K.M., Maddipati, K.R., and Birkmeier, J. Interference in enzyme immunoassays. J Clin Immunoassay 15 116-120 (1992).

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).

Baskaya, M.K., Hu, Y., Donaldson, D., et al. Protective effect of the 5-lipoxygenase inhibitor AA-861 on cerebral edema after transient ischemia. J Neurosurg 85 112-116 (1996).

Janabi, N., Chabrier, S., and Tardieu, M. Endogenous nitric oxide activates prostaglandin F_2α production in human microglial cells but not in astrocytes. A study of interactions between eicosanoids, nitric oxide, and superoxide anion (O₂-) regulatory pathways. J Immunol 157 2129-2135 (1996).

Huebner, J.M., Eversole, R.R., Jackson, W.F., et al. Leukotriene C₄ biosynthesis in isolated August rat peritoneal leukocytes. Mediators Inflamm 5 443-447 (1996).

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).

Roshak, A., Sathe, G., and Marshall, L.A. Suppression of monocyte 85-kDa phospholipase A₂ by antisense and effects of endotoxin-induced prostaglandin biosynthesis. J Biol Chem 269 25999-26005 (1994).

Mirzoeva, O.K., and Calder, P.C. The effect of propolis and its components on eicosanoid production during the inflammatory response. Prostaglandins Leukot Essent Fatty Acids 55 441-449 (1996).

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