title: Differential alveolar epithelial injury and protein expression in pneumococcal pneumonia.
abstract: The integrity of the alveolar epithelium is a key factor in the outcome of acute lung injury. Here, we investigate alveolar epithelial injury and the expression of epithelial-selective markers in Streptococcus pneumoniae-induced acute lung injury. S. pneumoniae was instilled into rat lungs and alveolar type I (RTI(40)/podoplanin, MMC6 antigen) and alveolar type II (MMC4 antigen, surfactant protein D, pro-surfactant protein C, RTII(70)) cell markers were quantified in lavage fluid and lung tissue at 24 and 72 hours. The alveolar epithelium was also examined using electron, confocal, and light microscopy. S. pneumoniae induced an acute inflammatory response as assessed by increased total protein, SP-D, and neutrophils in lavage fluid. Biochemical and morphological studies demonstrated morphologic injury to type II cells but not type I cells. In particular, the expression of RTI(40)/podoplanin was dramatically reduced, on the surface of type I cells, in the absence of morphologic injury. These data demonstrate that type II cell damage can occur in the absence of type I cell injury without affecting the ability of the lung to return to a normal morphology. These data also demonstrate that RTI(40)/podoplanin is not a type I cell phenotypic marker in experimental acute lung injury caused by S. pneumoniae. Given that RTI(40)/podoplanin is an endogenous ligand for the C-type lectin receptor and this receptor plays a role in platelet aggregation and neutrophil activation, we hypothesize that the reduction of RTI(40)/podoplanin on type I cells might be important for the regulation of platelet and/or neutrophil function in experimental acute lung injury.
authors.affiliation: MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Tyrrell
authors.forename: Stuart R
authors.initials: SR
authors.lastname: McKechnie
authors.forename: Michael F
authors.initials: MF
authors.lastname: Beers
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Mitchell
authors.forename: Mary C
authors.initials: MC
authors.lastname: McElroy
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D051402:Aquaporin 5 / Q000235:genetics / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010974:Platelet Aggregation / Q000235:genetics; D011018:Pneumonia, Pneumococcal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013296:Streptococcus pneumoniae; D000098853:Podoplanin
chemical_list: D000954:Antigens, Surface; D051402:Aquaporin 5; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D037663:Pulmonary Surfactant-Associated Protein D; C496040:Aqp5 protein, rat; C092025:Pdpn protein, rat; D000098853:Podoplanin