Effects of RSV infection on pulmonary surfactant protein SP-A in cultured human type II cells: contrasting consequences on SP-A mRNA and protein

Department of Pediatrics, The University of Texas Health Science Center at Houston, Houston, Texas Submitted 22 November 2004 ; accepted in final form 12 July 2005 Respiratory syncytial virus (RSV) is the most important cause of serious lower respiratory illness in infants and children. Surfactant proteins A (SP-A) and D (SP-D) play critical roles in lung defense against RSV infections. Alterations in surfactant protein homeostasis in the lung may result from changes in production, metabolism, or uptake of the protein within the lung. We hypothesized that RSV infection of the type II cell, the primary source of surfactant protein, may alter surfactant protein gene expression. Human type II cells grown in primary culture possess lamellar bodies (a type II cell-specific organelle) and the ability to express surfactant protein mRNA. These cells were infected with RSV (by morphology and antibody binding). Surfactant protein mRNA levels determined by quantitative RT-PCR indicated a marked increase in SP-A mRNA levels (3-fold) 24 h after RSV exposure, whereas SP-D mRNA levels were unaffected. In contrast to mRNA levels, total SP-A protein levels (determined by Western blot analysis) were decreased 40% after RSV infection. The percentage of secreted SP-A was 43% of the total SP-A in the RSV-infected cells, whereas the percentage of secreted SP-A was 61% of the total SP-A in the uninfected cells. These changes in SP-A transcript levels and protein secretion in cultured human cells were recapitulated in RSV-infected mouse lung. Our findings suggest that type II cells are potentially important targets of RSV lower respiratory infection and that alterations in surfactant protein gene expression and SP-A protein homeostasis in the lung may arise via direct effects of RSV. surfactant protein A; respiratory syncytial virus; alveolar type II cell Address for reprint requests and other correspondence: J. L. Alcorn, Jr., Dept. of Pediatrics, The Univ. of Texas-Houston Medical School, 6431 Fannin, Suite 3.222, Houston, TX 77030 (e-mail: joseph.l.alcorn{at}uth.tmc.edu )