Recombinant plasma gelsolin diminishes the acute inflammatory response to hyperoxia in mice.
BACKGROUND
The acute respiratory distress syndrome remains a common and poorly understood complication of a variety of insults. Ventilation with high concentrations of inspired oxygen may further damage already compromised lungs. By scavenging extracellular actin and modulating the effects of lysophosphatidic acid, plasma gelsolin could serve a critical protective role against oxidant injury.


METHODS
Mice exposed to >95% O2 for a total of 72 hours were treated with gelsolin or albumin after 24 and 48 hours.


RESULTS
Neutrophil counts in bronchoalveolar fluid rose (P=0.0002) and gelsolin levels dropped (P<0.00001) in mice with acute hyperoxic lung injury. The acute inflammatory response to hyperoxia was significantly reduced in the gelsolin- compared with the bovine serum albumin-treated mice (P=0.03).


CONCLUSIONS
These data imply that i) gelsolin depletion contributes to the pathogenesis of oxygen toxicity and ii) repletion of gelsolin can partially abrogate the resultant exudative response.
Christofidou-Solomidou
Melpo
M
Division of Pulmonary Medicine, Department of Medicine, University of Pennsylvania Medical School, Philadelphia, USA.
Scherpereel
Arnaud
A
Solomides
Charalambos C
CC
Christie
Jason D
JD
Stossel
Thomas P
TP
Goelz
Susan
S
DiNubile
Mark J
MJ
D000818:Animals; D018260:Gelsolin / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D018496:Hyperoxia / Q000150:complications / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000097:blood
D018260:Gelsolin; D011994:Recombinant Proteins