Mechanisms responsible for surfactant changes in sepsis-induced lung injury.
Pulmonary surfactant is altered in sepsis, and these changes contribute to the predisposition of septic lungs to subsequent insults, ultimately leading to acute lung injury. Specifically, the total amount of surfactant is lower in sepsis, mainly due to decreased small aggregate (SA) surfactant pools. The amount of large aggregate (LA) surfactant is not altered. To evaluate the mechanisms responsible for these alterations, trace doses of tritium-labelled dipalmitoylphosphatidylcholine (3H-DPPC)-labelled LA were instilled intratracheally into adult rats 20 hrs after caecal ligation and perforation (CLP) or sham surgery. Animals were sacrificed at 0, 1 and 4 h after instillation and recovery of 3H-DPPC in alveolar macrophages (AM), LA and SA was measured. In separate in vitro experiments, AM isolated from CLP/sham rats were incubated with LA or SA isolated from normal animals to evaluate the uptake of these aggregates into the AM. Results showed increased surfactant radioactivity associated with AM of CLP animals compared with sham animals both in vivo and in vitro. In addition, more 3H-DPPC label remained in LA forms in the CLP animals in vivo compared with sham. These findings indicate that differences in surfactant aggregate uptake and large aggregate conversion occur in septic lungs, resulting in changes in surfactant pools.
Huang
W
W
Dept of Physiology, Pharmacology and Medicine, Lawson Health Research Institute, University of Western Ontario, London, ON N6A 4V2, Canada.
McCaig
L A
LA
Veldhuizen
R A W
RA
Yao
L-J
LJ
Lewis
J F
JF
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D050356:Lipid Metabolism / Q000502:physiology; D008171:Lung Diseases / Q000473:pathology* / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D011336:Probability; D037661:Pulmonary Surfactant-Associated Proteins / Q000032:analysis / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000473:pathology* / Q000503:physiopathology
D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine