Coexpression of RTI sub(40) with alveolar epithelial type II cell proteins in lungs following injury: identification of alveolar intermediate cell types

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 289; no. 3; pp. L382 - L390
• Main Authors: Clegg, Gareth R, Tyrrell, Christine, McKechnie, Stuart R, Beers, Michael F, Harrison, David, McElroy, Mary C
• Format: Journal Article
• Language: English
• Published: 01.09.2005
• Subjects: Staphylococcus
• ISSN: 1040-0605

Injured alveolar epithelial type (AT) I cells are replaced following the proliferation and transformation of ATII cells to new ATI cells. RTI sub(40) is an ATI cell-specific protein required for normal lung development. We hypothesized that intermediate cell types in the ATII-to-ATI cell transformation would coexpress RTI sub(40) and ATII cell-selective proteins. To test this hypothesis, we used a rat model of Staphylococcus aureus-induced acute lung injury and a panel of ATI and ATII cell-specific and -selective antibodies. S. aureus induced an acute inflammatory reaction that was resolving by day 3 postinoculation. At day 3 postinoculation, the alveolar wall was thickened secondary to ATII cell hyperplasia. With the use of confocal microscopy, there was a fivefold increase in the fractional surface area of alveolar walls stained with ATII cell membrane proteins (RTII sub(70) and MMC4) and a decrease in the fractional surface area associated with RTI sub(40)-expressing cells. S. aureus-treated lungs also contained unique cell types that coexpressed the RTI sub(40) and ATII markers RTI sub(40)/MMC4/RTII sub(70)- and RTI sub(40)/MMC4-positive cells. These cells were not observed in control lungs. RTI sub(40)/MMC4-positive cells were also found in cultured ATII cells before they transformed to an ATI-like phenotype. Our data suggest that RTI sub(40)/MMC4/RTII sub(70)- and RTI sub(40)/MMC4-positive cells are intermediates in the ATII-to-ATI cell transformation. These data also suggest that the coexpression of RTI sub(40) with ATII cell proteins may be used to identify and investigate ATII cell transdifferentiation to ATI cells following injury.