Sulfidopeptide-leukotriene peptidases in pulmonary edema fluid from patients with the adult respiratory distress syndrome

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 less than 0.005 and P less than 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 microliter 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 degrees 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.

Lipid storm within the lungs of severe COVID-19 patients: Extensive levels of cyclooxygenase and lipoxygenase-derived inflammatory metabolites

“…As a starting point, we investigated eicosanoids derived from the cyclooxygenase (COX) pathway. Our working hypothesis was that some COX metabolites would be increased, considering that IL-1β levels are elevated in the BALs of some COVID-19 patients (16) Leukotrienes are also potent bioactive lipids previously documented to regulate the inflammatory responses in the airway/lung in diseases, notably ARDS (20,21). As such, their involvement in the pathogenesis of COVID-19 has recently been postulated even though their levels were unknown (22).…”

5-Lipoxygenase Deficiency Prevents Respiratory Failure during Ventilator-induced Lung Injury

“…LT concentrations have been reported to be elevated in other experimental models of acute lung injury (22,27). Moreover, increased levels of LTs have been detected in pulmonary edema fluid obtained from patients with ARDS (23)(24)(25). LTs are primarily synthesized by activated cells of myeloid origin, such as neutrophils, eosinophils, mast cells, and monocytes/macrophages (26).…”

“…LTs have been implicated as inflammatory mediators in experimental models of acute lung injury (22) and were found to be elevated in pulmonary edema fluid obtained from patients with ARDS (23)(24)(25). Moreover, cysLTs appear to play a critical role in mediating neutrophil-dependent inflammation (26).…”

Chronic Sidestream Cigarette Smoke Exposure Causes Lung Injury in Rabbits

“…However, this injury was not consistent, and it was considered that the bronchial clearance of 99mTcDTPA constitutes a large enough portion of total pulmonary clearance to be responsible for the increase in 99-TcDTPA lung uptake observed in the SSCS rabbits. Many investigators have demonstrated that sulfidopeptide leukotrienes, mainly LTC4 and LTD4, can increase vascular permeability [17][18][19][20]; but the possibility that LTE4 can also cause increased permeability in alveolar epithelial cells cannot be dismissed.…”