Sulfidopeptide-leukotriene peptidases in pulmonary edema fluid from patients with the adult respiratory distress syndrome |
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Authors: | W. D. Ratnoff M. A. Matthay M. Y. S. Wong Y. Ito K. H. Vu J. Wiener-Kronish E. J. Goetzl |
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Affiliation: | (1) Howard Hughes Medical Institute and Department of Medicine, University of California Medical Center, 94143-0724 San Francisco, California;(2) Cardiovascular Research Institute and Department of Medicine, University of California Medical Center, 94143-0120 San Francisco, California;(3) Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan |
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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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Keywords: | Leukotriene arachidonic acid peptidase pulmonary edema respiratory failure |
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