Changes in plasma gelsolin concentration during acute oxidant lung injury in mice.
Oxidant stress may contribute to acute lung injury under some circumstances. The rapid depletion of plasma gelsolin following major trauma in patients who subsequently develop respiratory distress suggests that this actin-scavenging protein might protect against delayed pulmonary complications. The specific aim of these experiments was to explore the temporal and quantitative relationship between gelsolin levels and lung damage. Gelsolin levels were measured in three murine models of oxidant injury: immunotargeting of pulmonary endothelium with an H2O2-generating enzyme; continuous exposure to >95% O2; and single high-dose thoracic radiation. The degree of lung injury was inversely related to gelsolin levels in mice treated with glucose oxidase-conjugated antibodies against platelet endothelial cell adhesion molecule-1 (p <0.0001). By 60-72 hours of hyperoxic exposure, gelsolin levels had dropped precipitously in all mice who sustained major lung damage (p <0.0001), establishing a quantitative association between gelsolin concentration and hyperoxic lung injury (r = -0.72; 95% confidence interval: ?0.81 to ?0.59). Gelsolin levels modestly but progressively fell in irradiated mice over the 3 days following treatment (p = 0.012) despite the development of only microscopic lung damage during this timeframe. These findings are consistent with the hypothesis that gelsolin depletion is involved in the pathogenesis of acute oxidant lung injury.
Christofidou-Solomidou
M
M
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania Medical School, Philadelphia, PA 19486, USA.
Scherpereel
A
A
Solomides
C C
CC
Muzykantov
V R
VR
Machtay
M
M
Albelda
S M
SM
DiNubile
M J
MJ
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004307:Dose-Response Relationship, Radiation; D018260:Gelsolin / Q000097:blood*; D005949:Glucose Oxidase / Q000008:administration & dosage / Q000009:adverse effects; D018496:Hyperoxia / Q000097:blood / Q000150:complications / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D008168:Lung / Q000528:radiation effects*; D055370:Lung Injury; D051379:Mice; D008807:Mice, Inbred BALB C; D016877:Oxidants / Q000009:adverse effects* / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000008:administration & dosage / Q000009:adverse effects; D011506:Proteins / Q000378:metabolism; D011829:Radiation Dosage; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000209:etiology*; D013223:Statistics as Topic; D013997:Time Factors
D018260:Gelsolin; D007074:Immunoglobulin G; D016877:Oxidants; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011506:Proteins; D005949:Glucose Oxidase