Lung heme oxygenase-1 is elevated in acute respiratory distress syndrome.
OBJECTIVE
We aimed to quantify concentrations of inducible heme oxygenase (HO)-1 in the lungs of patients with acute respiratory distress syndrome (ARDS) and to investigate its role as a source of ferrous iron and as a signaling agent for iron regulation. Control of such processes by heme oxygenase has implications for the onset, progression, and resolution of ARDS.


METHODS
Retrospective analysis of archived samples.


METHODS
Adult intensive care unit of a postgraduate teaching hospital.


METHODS
Patients admitted to the adult intensive care unit who fulfilled the American-European Consensus Conference criteria for ARDS.


METHODS
Biochemical and immunohistochemical studies using bronchoalveolar lavage fluid or lung tissue were performed in patients with established ARDS and in those undergoing lung resection (controls).


RESULTS
Concentrations of heme oxygenase protein were significantly elevated in lung tissue (193.7 +/- 13.27 vs. 81.0 +/- 16.0%, p < .01) and in bronchoalveolar lavage fluid (2.4 x 10(5) vs. 1.4 x 10(5) densitometric units, p = .047) taken from patients with ARDS compared with controls. Concentrations of heme oxygenase protein in bronchoalveolar lavage fluid from patients with ARDS correlated positively and significantly with changes in the concentrations of ferritin (r = .697, p = .02) and the iron saturation of transferrin (r = .8, p = .014) but correlated negatively and significantly with concentrations of bleomycin-detectable (redox-active) iron (r = -.73, p = .031). Significantly elevated (p < .05) concentrations of heme oxygenase staining in cell types expressing this protein were detected in patients with ARDS, compared with concentrations in the same cells taken from controls undergoing lung resection.


CONCLUSIONS
Heme oxygenase protein is elevated in the lungs of patients with ARDS and may contribute to the changes in iron mobilization, signaling, and regulation seen in this condition.
Mumby
Sharon
S
Unit of Critical Care, Imperial College Faculty of Medicine, Royal Brompton Hospital, Sydney Street, London, UK.
Upton
Rebecca L
RL
Chen
Yan
Y
Stanford
Salome J
SJ
Quinlan
Gregory J
GJ
Nicholson
Andrew G
AG
Gutteridge
John M C
JM
Lamb
Nicholas J
NJ
Evans
Timothy W
TW
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D015984:Causality; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000032:analysis / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis*; D051547:Heme Oxygenase-1; D006706:Homeostasis; D006784:Hospitals, Teaching; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007501:Iron / Q000032:analysis / Q000378:metabolism; D035925:Iron-Regulatory Proteins / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010084:Oxidation-Reduction; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D015398:Signal Transduction; D014168:Transferrin / Q000032:analysis / Q000378:metabolism
D035925:Iron-Regulatory Proteins; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1