Type XVIII collagen degradation products in acute lung injury

Introduction: In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge. Methods: Endostatin was measured by ELISA and western blotting. Results: Endostatin is elevated within the plasma and bronchoalveolar lavage fluid of patients with acute lung injury. Lavage endostatin reflected the degree of alveolar neutrophilia and the extent of the loss of protein selectivity of the alveolar-capillary barrier. Plasma levels of endostatin correlated with the severity of physiological derangement. Western blotting confirmed elevated type XVIII collagen precursor levels in the plasma and lavage and multiple endostatin-like fragments in the lavage of patients. One lung ventilation and LPS challenge rapidly induce increases in lung endostatin levels. Conclusions: Endostatin may adversely affect both alveolar barrier endothelial and epithelial cells, so its presence within both the circulation and the lung may have a pathophysiological role in acute lung injury that warrants further evaluation

Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome

Background Kerbs von Lungren 6 antigen (KL-6) is expressed on the surface of alveolar type II cells, and elevated plasma and epithelial lining fluid levels of KL-6 have previously been shown to correlate with the severity of disease and survival in acute respiratory distress syndrome (ARDS). The relationship between alveolar inflammation and KL-6 measurements has not been ascertained. We hypothesized that the elevation of KL-6 in ARDS is dependent upon the severity of neutrophilic inflammation. Furthermore we were interested in the relationship between significant alveolar infection and KL-6 levels. Methods Plasma arterial samples were collected from ARDS patients on day 1 and when possible on day 4 along with bronchoalveolar lavage fluid (BALF) samples on the same day. Bacterial growth in the BALF was determined by quantitative cultures and was defined as significant at counts >1 × 104 colony-forming units. Results Plasma KL-6 levels in ARDS patients were elevated compared with at-risk control individuals (P = 0.014) and with normal control individuals (P = 0.02). The plasma KL-6 level correlated with the Murray Lung Injury Score (r = 0.68, P = 0.001) and with BALF KL-6 (r = 0.3260, P = 0.04). The BALF KL-6 level was detectable in all ARDS cases and was lower on both day 0 and day 4 in those who survived. BALF KL-6 also correlated with the BALF myeloperoxidase activity (r = 0.363, P = 0.027), with the BALF cell count per millilitre (r = 0.318, P = 0.038), with BALF epithelial-cell-derived neutrophil attractant 78; (r = 0.37, P = 0.016) and with BALF vascular endothelial growth factor (r = 0.35, P = 0.024). The BALF KL-6 level of ARDS patients with significant pathogenic bacterial growth was similar compared with those without significant infection. Conclusion KL-6 may represent a useful marker of alveolar type II cell dysfunction in ARDS since the levels reflect the severity of lung injury and neutrophilic inflammation. KL-6 release across the alveolar epithelial barrier is associated with a poor prognosis. The pathophysiological roles of KL-6 in the development of ARDS warrant further study

Kerbs von Lungren 6 antigen correlation with bronchoalveolar lavage fluid cell count and myeloperoxidase activity

Bronchoalveolar lavage fluid (BALF) Kerbs von Lungren 6 antigen (KL-6) levels correlate with the BALF cell count per millilitre (= 0.318, = 0.038) and the BALF myeloperoxidase activity (= 0.363, = 0.027) in patients with acute respiratory distress syndrome.<p><b>Copyright information:</b></p><p>Taken from "Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome"</p><p>http://ccforum.com/content/12/1/R12</p><p>Critical Care 2008;12(1):R12-R12.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2374609.</p><p></p

Kerbs von Lungren 6 antigen levels in plasma and in bronchoalveolar lavage fluid

Plasma and bronchoalveolar lavage fluid (BALF) levels of Kerbs von Lungren 6 antigen (KL-6) are persistently elevated in acute respiratory distress syndrome (ARDS) patients compared with normal and at-risk individuals. Plasma levels measured by ELISA.<p><b>Copyright information:</b></p><p>Taken from "Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome"</p><p>http://ccforum.com/content/12/1/R12</p><p>Critical Care 2008;12(1):R12-R12.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2374609.</p><p></p

Correlation of Kerbs von Lungren 6 antigen with bronchoalveolar lavage fluid chemokine levels

Bronchoalveolar lavage fluid (BALF) Kerbs von Lungren 6 antigen (KL-6) correlates with BALF epithelial-cell-derived neutrophil attractant 78 (ENA-78) (= 0.37, = 0.016) and BALF vascular endothelial growth factor (VEGF) (= 0.35, = 0.024).<p><b>Copyright information:</b></p><p>Taken from "Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome"</p><p>http://ccforum.com/content/12/1/R12</p><p>Critical Care 2008;12(1):R12-R12.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2374609.</p><p></p