Biochemical detection of type I cell damage after nitrogen dioxide-induced lung injury in rats.
We have previously shown that injury to lung epithelial type I cells can be detected biochemically by measuring the airway fluid content of a type I cell-specific protein, rTI40, in a model of severe acute lung injury [M. C. McElroy, J.-F. Pittet, S. Hashimoto, L. Allen, J. P. Wiener-Kronish, and L. G. Dobbs. Am. J. Physiol. 268 (Lung Cell. Mol. Physiol. 12): L181-L186, 1995]. The first objective of the present study was to evaluate the utility of rTI40 in the assessment of alveolar injury in a model of milder acute lung injury. Rats were exposed to 18 parts/ million NO2 for 12 h; control rats received filtered air for 12 h. In NO2-exposed rats, the total amount of rTI40 in bronchoalveolar fluid was elevated 2-fold compared with control values (P < 0.001); protein concentration was 8.5-fold of control values (P < 0.001). The increase in rTI40 was associated with morphological evidence of injury to type I cells limited to the proximal alveolar regions of the lung. The second objective was to correlate the severity of alveolar type I cell injury with functional measurements of lung epithelial barrier integrity. NO2 inhalation stimulated distal air space fluid clearance despite a significant increase in lung endothelial and epithelial permeability to protein. These data demonstrate that rTI40 is a useful biochemical marker for mild focal injury and that exposure to NO2 alters lung barrier function. Taken together with our earlier studies, these results suggest that the quantity of recoverable rTI40 can be used as an index of the severity of damage to the alveolar epithelium.
McElroy
M C
MC
Cardiovascular Research Institute, University of California, San Francisco 94143, USA.
Pittet
J F
JF
Allen
L
L
Wiener-Kronish
J P
JP
Dobbs
L G
LG
D000818:Animals; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009585:Nitrogen Dioxide / Q000633:toxicity*; D011506:Proteins / Q000032:analysis*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098853:Podoplanin
D015415:Biomarkers; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009585:Nitrogen Dioxide; D011506:Proteins; C092025:Pdpn protein, rat; D000098853:Podoplanin