Type XVIII collagen degradation products in acute lung injury.
BACKGROUND
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.
Lung Injury and Fibrosis Treatment Program (LIFT), Department of Medical Sciences, The Medical School University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Gavin D
GD
Perkins
Nazim
N
Nathani
Alex G
AG
Richter
Daniel
D
Park
Murali
M
Shyamsundar
Ritva
R
Heljasvaara
Taina
T
Pihlajaniemi
Mav
M
Manji
W
W
Tunnicliffe
Danny
D
McAuley
Fang
F
Gao
David R
DR
Thickett
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid; D043170:Collagen Type XVIII / Q000378:metabolism*; D043169:Endostatins / Q000097:blood; D004739:England; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D014508:Urea
D043170:Collagen Type XVIII; D043169:Endostatins; D014508:Urea