Oxidatively modified proteins in bronchoalveolar lavage fluid of patients with ARDS and patients at‐risk for ARDS

Abstract

Oxidative stress in acute respiratory distress syndrome (ARDS) is considered as an important pathophysiological mechanism in acute impairment of lung function. The present study investigated whether a pulmonary oxidant±antioxidant imbalance is indicated by substantial oxidative modification of proteins in bronchoalveolar lavage (BAL) fluid.Oxidatively modified proteins in BAL fluid, as measured by the reduction of protein carbonyl groups with tritiated borohydride, were studied in control subjects, patients with clinically established ARDS, and patients considered at-risk for ARDS because they had had coronary bypass surgery. Subsets of these at-risk patients were pretreated either with methylprednisolone or N-acetylcysteine.The carbonyl content of BAL fluid proteins was greatly increased in ARDS patients (5.0 1.3 nmol carbonyl . mL -1 BAL fluid; mean SEM; p=0.0004; n=10) and moderately increased in the untreated patients at-risk for ARDS (1.3 0.2 nmol . mL -1 ; p=0.027; n=19) compared with controls (0.8 0.2 nmol . mL -1 ; n=12). The two other at-risk groups pretreated either with methylprednisolone or N-acetylcysteine showed carbonyl values that were statistically not different from the controls (1.2 0.2 nmol . mL -1 ; p=0.13; n=13, and 1.1 0.3 nmol . mL -1 ; p=0.40; n=8, respectively).These results show that oxidatively modified proteins clearly accumulated in bronchoalveolar lavage fluid of acute respiratory distress syndrome patients, and to a minor extent in untreated at-risk patients. These data suggest a severe oxidant± antioxidant imbalance in acute respiratory distress syndrome. Eur Respir J 1999; 13: 169±174. Many pulmonary diseases, including the acute respiratory distress syndrome (ARDS), chronic bronchitis/emphysema, asthma, and interstitial pulmonary fibrosis [1±3] have been associated with an excess of reactive oxygen species (ROS). Patients undergoing cardiopulmonary bypass (CPB) surgery have an elevated risk of developing ARDS [4] and also appear to be under oxidative stress [5]. In ARDS patients and patients at-risk for ARDS, the epithelial lining fluid (ELF) recovered as bronchoalveolar lavage (BAL) fluid is characterized by increased numbers of neutrophils [6] that are known to be potent in generating superoxide anions. BAL fluid of ARDS patients and at-risk patients contains a variety of cytokines [6,7] as well as lipid mediators [8] that are known to prime or activate neutrophils for oxidant production. Substantial lack of the antioxidant glutathione (GSH) in the respiratory tract of ARDS patients as described by BUNNELL and PACHT [9] may enhance the risk for oxidant injury. The delicate balance between oxidant and antioxidant systems, however, is of major importance for maintaining normal lung function and structure. In the plasma of ARDS patients and patients at-risk for ARDS, oxidative stress was concluded from the formation of lipid peroxidation products [5,10], and protein oxidation [5,11]. However, the situation in plasma does not necessarily reflect the situation in the l...

Septic pulmonary microvascular endothelial cell injury: role of alveolar macrophage NADPH oxidase

“…Moreover, pharmacological reduction of pulmonary protein leak in ALI is associated with a reduction in lipid peroxidation (32). There also is evidence of protein oxidation in ALI, including accumulation of protein carbonyl groups in the BAL of patients with ALI (26). ROS, such as H 2 O 2 , also have been shown to directly induce EC barrier dysfunction through the modification of various cytoskeletal and junction proteins, including VE-cadherin, and formation of inter-EC gaps (5,39,49,56).…”

The Role of Oxidative Stress Markers in Developing of Acute Respiratory Distress Syndrome / Oksidatîvâ Stresa Marķieru Loma Akûta Respiratora Distresa Sindroma Attîstîbâ

“…Increased concentrations of protein carbonyls have been documented in ARDS patients (Sittipunt et al, 2001). The carbonyl content of broncho-alveolar lavage (BAL) fluid proteins were observed to be significantly increased in patients with diagnosed ARDS (5.0 F 1.3 nmol carbonyl/ml BAL fluid, p = 0.0004) and moderately increased in patients at risk for de-veloping ARDS caused by coronary bypass surgery (1.3 F 0.2 nmol/ ml, p = 0.027), compared with a control group (0.8 F 0.2 nmol/ ml) (Lenz et al, 1999). In addition, there are a large number of potential oxidative modifications, of which only a few have been systematically studied, for example the already mentioned protein carbonyl group products.…”

Nutrition and Oxidants in the Critically Ill Patient

“…21 In addition, oxidatively modified proteins accumulate in the bronchoalveolar lavage fluid of ARDS patients, indicating a severe oxidant-antioxidant imbalance. 25 Measurements of high protein-carbonyl concentrations in plasma, as well as bronchial aspirates, indicate that oxidation occurs early and may impair cell signaling. 25 This increase in modified proteins correlates with myeloperoxidase (MPO) levels, confirming that the primary source of the oxidant stress is the PMNL.…”

“…25 Measurements of high protein-carbonyl concentrations in plasma, as well as bronchial aspirates, indicate that oxidation occurs early and may impair cell signaling. 25 This increase in modified proteins correlates with myeloperoxidase (MPO) levels, confirming that the primary source of the oxidant stress is the PMNL. 26 Reactive oxidants may also initiate inflammatory responses by inducing an autoimmune process.…”