Research
Type XVIII collagen degradation products in acute lung injury
- † Equal contributors
1 Lung Injury and Fibrosis Treatment Program (LIFT), Department of Medical Sciences, The Medical School University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
2 Collagen Research Unit, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, FIN-90014, Finland
3 Department of Intensive Care, University Hospital Birmingham, Edgbaston, Birmingham, B15 2TH, UK
4 Department of Anaesthesia and Intensive Care, Birmingham Heartlands Hospital, Birmingham, B9 5SS, UK
5 Respiratory Medicine Research Cluster, Centre for Infection and Immunity, Microbiology Building, The Queen's University of Belfast, Grosvenor Road, Belfast, BT12 6BN, Northern Ireland, UK
6 Lung Investigation Unit, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK
Critical Care 2009, 13:R52 doi:10.1186/cc7779
Published: 9 April 2009Abstract
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.
