Abstract
The human pulmonary edema fluid concentrations of LTC4 and of LTD4 and LTE4, derived peptidolytically from LTC4, were assessed by radioimmunoassays of the mediators resolved by reverse-phase high-performance liquid chromatography. The mean pulmonary edema fluid concentration (± SD) of LTD4 of 19.2±25.6 nM for 12 patients with the adult respiratory distress syndrome and of LTE4 of 192±309 nM for 10 of the patients were significantly higher (P<0.005 andP<0.05) than those of 2.2±2.4 and 11.0±18.2 nM, respectively, for 10 patients with cardiogenic pulmonary edema, whereas the lower mean concentrations of LTC4 were not significantly different for the two groups. Pulmonary edema fluid from five patients with adult respiratory distress syndrome, one with cardiogenic pulmonary edema, and one with an indeterminate syndrome contained similar concentrations of peptidoleukotriene peptidases. The LTC4 and LTD4 peptidolytic activities in ARDS fluids were 81 and 142 kD, respectively, by gel filtration. The extents of peptidolysis of [3]LTC4 and [3]LTD4 by 100 µl of pulmonary edema fluid attained respective mean maximum levels of 74.5±2.9% (N=5) and 37.7±10.2% (N=4) after 30 min at 37°C and were inhibited by serine-borate and by cysteine, respectively. The predominance of LTD4 and LTE4 over LTC4 in states of altered pulmonary vascular pressure and permeability thus is attributable to two distinct peptidases.
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Staub NC: Pulmonary edema due to increased microvascular permeability to fluid and protein. Circ Res 43:143–151, 1978
Anderson RR, Holliday RL, Driedger AA, Lefcoe M, Reid B, Sibbald WJ: Documentation of pulmonary capillary permeability in the adult respiratory distress syndrome accompanying human sepsis. Am Rev Resp Dis 119:869–877, 1979
Brigham KL, Kariman K, Harris TR, Snapper JR, Bernard GR, Young SL: Correlation of oxygenation with vascular permeability-surface area but not with lung water in humans with acute respiratory failure and pulmonary edema. J Clin Invest 72:339–349, 1983
Montaner JSG, Tsang J, Evans KG, Mullen JBM, Burns AR, Walker DC, Wiggs B, Hogg JC: Alveolar epithelial damage. A critical difference between high pressure and oleic acid-induced low pressure pulmonary edema. J Clin Invest 77:1786–1796, 1986
Heflin AC, Brigham KL: Prevention by granulocyte depletion of increased vascular permeability of sheep lungs following endotoxemia. J Clin Invest 68:1253–1260, 1981
Zimmerman GA, Renzetti AD, Hill HR: Functional and metabolic activity of granulocytes from patients with the adult respiratory distress syndrome. Am Rev Resp Dis 127:290–300, 1983
Hammarschmidt DE, White JG, Craddock PR, Jacobs HS: Corticosteroids inhibit complement-induced granulocyte aggregation. J Clin Invest 63:789–796, 1979
Till, GO, Johnson KJ, Kunkel R, Ward PA: Intravascular activation of complement and acute lung injury. Dependency on neutrophils and oxygen metabolites. J Clin Invest 69:1126–1135, 1982
Weinberg PF, Matthay MA, Webster RO, Roskos KV, Goldstein IM, Murray JF: Biologically active products of complement and acute lung injury in patients with the sepsis syndrome. Am Rev Resp Dis 130:791–796, 1984
Brigham KL, Duke SS: Prostaglandins in lung disease: Adult respiratory distress syndrome. Semin Resp Med 7:11–16, 1985
Voelkel NF, Simpson J, Worthen S, Reeves JT, Henson PM, Murphy RC: Platelet-activating factor causes pulmonary vasoconstriction and edema via platelet-independent leukotriene formation.In Advances in Prostaglandin, Thromboxane, and Leukotriene Research, B Samuelsson, R Paoletti, P Ramwell (eds). New York, Raven Press, 1983, pp 179–183
Dahlen SE, Bjork J, Hedqvist P, Arfors KE, Hammarstrom S, Lindgren JA, Samuelsson B: 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
Worthen GS, Haslett C, Smedly LA, Rees AJ, Gumbay RS, Henson JE, Henson PE: Lung vascular injury induced by chemotactic factors: Enhancement by endotoxins. Fed Proc 45:7–12, 1986
Till GO, Ward PA: Systemic complement activation and acute lung injury. Fed Proc 45:13–18, 1986
Meyrick BO: Endotoxin-mediated pulmonary endothelial cell injury. Fed Proc 45:19–24, 1986
Stevens JH, O'Hanley P, Shapiro JM, Mihm FG, Satoh PS, Collins JA, Raffin TA: Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. J Clin Invest 77:1812–1816, 1986
Burghuber OC, Strife RJ, Zirrolli J, Henson PM, Henson JE, Mathias MM, Reeves JT, Murphy RC, Voelkel NF: Leukotriene inhibitors attenuate rat lung injury induced by hydrogen peroxide. Am Rev Resp Dis 131:778–785, 1985
Lewis RA, Austen KF, Drazen JM, Clark DA, Marfat A, Corey EJ: Slow-reacting substance of anaphylaxis: Identification of leukotrienes C-1 and D from human and rat sources. Proc Natl Acad Sci USA 77:3710–3715, 1980
Damon M, Chavis C, Godard PH, Michael RB, Crastes de Paulet A: Purification and mass spectrometry identification of leukotriene D4 synthesized by human alveolar macrophages. Biochem Biophys Res Commun 111:518–524, 1983
Albert RK, Greenberg GM, Henderson W: Leukotriene C4 and D4 increase pulmonary vascular permeability in excised rabbit lungs. Chest (Suppl) 5:85S-86S, 1983
Kadowitz PJ, Hyman AL: Analysis of responses to leukotriene D4 in the pulmonary vascular bed. Circ Res 55:707–717, 1984
Drazen JM, Austen KF, Lewis RA, Clark DA, Goto G, Marfat A, Corey EJ: Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc Natl Acad Sci USA 77:4354–4358, 1980
Lewis RA, Drazen JM, Austen KF, Clark DA, Corey EJ: Identification of the C(6)-S-conjugate of leukotriene A with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS-A). Importance of the 11-cis-geometry for biological activity. Biochem Biophys Res Commun 96:271–277, 1980
Soter NA, Lewis RA, Corey EJ, Austen KF: Local effects of synthetic leukotrienes (LTC4, LTD4, LTE4, and LTB4) in human skin. J Invest Dermatol 80:115–119, 1983
Matthay MA, Eschenbacher WL, Goetzl EJ: Elevated concentrations of leukotriene D4 in pulmonary edema fluid of patients with the adult respiratory distress syndrome. J Clin Immunol 4:479–483, 1984
Rodkey FL: Direct spectrophotometric determination of albumin in human serum. Clin Chem 11:478–487, 1965
Cannon DC, Olitzky I, Inkpen JA: Proteins.In Clinical Chemistry: Principles and Technics, 2nd ed., RJ Henry, DC Cannon, JW Winkelman (eds). Hagerstown, Harper & Row, 1974, pp 405–502
Paterson NAM, McIver DJL, Schurch S: Zymosan enhances leukotriene D4 metabolism by porcine alveolar macrophages. Immunology 56:153–159, 1985
Zar JH: Biostatistical Analysis, 2 ed. Englewood Cliffs, NJ, Prentice-Hall, 1984
Sok DE, Pai JK, Atrache V, Kang YC, Sih CJ: Enzymatic inactivation of SRS-Cys-Gly (leukotriene D). Biochem Biophys Res Commun 101:222–229, 1981
Snyder DW, Aharony D, Dobson P, Tsai BS, Krell RD: Pharmacological and biochemical evidence for metabolism of peptide leukotrienes by guinea-pig airway smooth muscle in vitro. J Pharmacol Exp Ther 231:224–229, 1984
Snyder DW, Krell RD: Pharmacological evidence for a distinct leukotriene C4 receptor in guinea pig trachea. J Pharmacol Exp Ther 231:616–622, 1984
Tate SS, Meister A: Serine-borate complex as a transition state inhibitor of gamma-glutamyl transpeptidase. Proc Natl Acad Sci USA 75:4806–4809, 1978
Orning L, Hammarstrom S: Inhibition of leukotriene C and leukotriene D biosynthesis. J Biol Chem 255:8023–8026, 1980
Cheng JB, Tounley RG: Effect of the serine-borate complex on the relative ability of leukotriene C4, D4, and E4 to inhibit lung and brain [3H]leukotriene D4 and [3H]leukotriene C4 binding: Demonstration of the agonists' potency order for leukotriene D4 and C4 receptors. Biochem Biophys Res Commun 119:612–617, 1984
Ito Y, Iwaki M, Ogiso T, Hirano K, Sugiura M, Sawaki S, Sugiura K: Differential determination of human liver and pancreas dipeptidase activities by using specific antibody-conjugated paper disks. Chem Pharm Bull 34:1176–1183, 1986
Swerdlow BN, Mihm FG, Goetzl EJ, Matthay MA: Leukotrienes in pulmonary edema fluid after cardiopulmonary bypass. Anesth Analg 65:306–308, 1986
Parker CW, Koch D, Huber MM, Falkenheim SF: Formation of the cysteinyl form of slow reacting substance (leukotriene E4) in human plasma. Biochem Biophys Res Commun 97:1038–1046, 1980
Koller M, Schonfeld W, Knoller J, Bremm KD, Konig W, Spur B, Crea A, Peters W: The metabolism of leukotrienes in blood plasma studied by high-performance liquid chromatography. Biochem Biophys Acta 833:128–134, 1985
Morris HR, Taylor GW, Jones CM, Piper PJ, Samhoun MN, Tippins JR: Slow reacting substances (leukotrienes): Enzymes involved in their biosynthesis. Proc Natl Acad Sci USA 79:4838–4842, 1982
Tate SS, Meister A: Identity of maleate-stimulated glutaminase with gamma-glutamyl transpeptidase in rat kidney. J Biol Chem 250:4619–4627, 1975
Kozak EM, Tate SS: Glutathione-degrading enzymes of microvillus membranes. J Biol Chem 257:6322–6327, 1982
Bernstrom K, Hammarstrom S: Metabolism of leukotriene D4 by porcine kidney. J Biol Chem 256:9576–9582, 1981
Spater HW, Quintana N, Becker FF, Novikoff AB: Immunocytochemical localization of gamma-glutamyltransferase in induced hyperplastic nodules of rat liver. Proc Natl Acad Sci USA 80:4742–4746, 1983
Brom J, Raulf M, Stuning M, Spur B, Crea A, Bremm KD, Konig W: Subcellular localization of enzymes involved in leukotriene formation within human polymorphonuclear leukocytes. Immunology 51:571–583, 1984
Raulf M, Stuning M, Konig W: Metabolism of leukotrienes by L-gamma-glutamyl-transpeptidase and dipeptidase from human polymorphonuclear granulocytes. Immunology 55:135–147, 1985
Lee CW, Lewis RA, Corey EJ, Austen KF: Conversion of leukotriene D4 to leukotriene E4 by a dipeptidase released from the specific granule of human polymorphonuclear leukocytes. Immunology 48:27–35, 1983
Campbell BJ, Forrester LJ, Zahler WL, Burks M: Beta lactamase activity of purified and partially characterized renal dipeptidase. J Biol Chem 259:14586–14590, 1984
Barouki R, Finidori J, Chobert MN, Aggerbeck M, Laperche Y, Hanoune J: Biosynthesis and processing of gamma-glutamyl transpeptidase in hepatoma tissue culture cells. J Biol Chem 259:7970–7974, 1984
Finidori J, Laperche Y, Haguenauer-Tsapis R, Barouki R, Guellaen G, Hanoune J: In vitro biosynthesis and membrane insertion of gamma-glutamyl transpeptidase. J Biol Chem 259:4687–4690, 1984
Nash B, Tate SS: In vitro translation and processing of rat kidney gamma-glutamyl transpeptidase. J Biol Chem 259:678–685, 1984
Goetzl EJ, Austen KF: A neutrophil-immobilizing factor derived from human leukocytes. I. Generation and partial characterization. J Exp Med 136:1564–1580, 1972
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Ratnoff, W.D., Matthay, M.A., Wong, M.Y.S. et al. Sulfidopeptide-leukotriene peptidases in pulmonary edema fluid from patients with the adult respiratory distress syndrome. J Clin Immunol 8, 250–258 (1988). https://doi.org/10.1007/BF00916553
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DOI: https://doi.org/10.1007/BF00916553