Neutrophil-derived S100A12 in acute lung injury and respiratory distress syndrome.
OBJECTIVE
Both persistent accumulation and activation of neutrophils may contribute to the most severe form of acute lung injury, acute respiratory distress syndrome. We analyzed the expression of neutrophil-derived S100A12 and the proinflammatory receptor for advanced glycation end products (RAGE) in patients with acute respiratory distress syndrome. Additional in vivo and in vitro experiments were performed to further analyze the contribution of S100A12 to pulmonary inflammation.


METHODS
We included 14 patients with acute respiratory distress syndrome and eight controls. In addition, 16 healthy subjects were included in an experimental lipopolysaccharide challenge model.


METHODS
Concentrations of S100A12 and soluble RAGE were analyzed in bronchoalveolar lavage fluid. The expression of S100A12 and RAGE in lung biopsies from patients was analyzed by immunohistochemistry. S100A12 was also analyzed in bronchoalveolar lavage fluid from eight healthy subjects after challenge with lipopolysaccharide and compared with eight controls who received placebo inhalation. Effects of S100A12 on endothelial cells were analyzed in vitro.


RESULTS
Patients with acute respiratory distress syndrome had significantly enhanced pulmonary S100A12 expression and higher S100A12 protein concentrations in bronchoalveolar lavage fluid than controls. Levels of soluble RAGE were not significantly elevated in acute respiratory distress syndrome. S100A12 concentrations decreased with time from disease onset. In healthy volunteers, S100A12 was elevated in bronchoalveolar lavage fluid after lipopolysaccharide inhalation. In vitro experiments confirmed strong proinflammatory effects of human S100A12.


CONCLUSIONS
S100A12 and its receptor RAGE are found at high concentrations in pulmonary tissue and bronchoalveolar lavage fluid in acute lung injury. S100A12 expression may reflect neutrophil activation during lung inflammation and contribute to pulmonary inflammation and endothelial activation via binding to RAGE.
Wittkowski
Helmut
H
Department of Pediatrics, Interdisciplinary Center of Clinical Research, Institute of Experimental Dermatology, University of Muenster, Germany.
Sturrock
Anne
A
van Zoelen
Marieke A D
MA
Viemann
Dorothee
D
van der Poll
Tom
T
Hoidal
John R
JR
Roth
Johannes
J
Foell
Dirk
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D009418:S100 Proteins / Q000032:analysis / Q000096:biosynthesis*; D000067616:S100A12 Protein; D015854:Up-Regulation
D008070:Lipopolysaccharides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human