Published ahead of print on August 17, 2006, doi:10.1165/rcmb.2006-0049OC Am. J. Respir. Cell Mol. Biol., Volume 36, Number 1, January 2007, 103-113 A more recent version of this article appeared on January 1, 2007
Submitted on January 31, 2006 Surfactant Dysfunction in SP-A(-/-) and iNOS (-/-) Mice with Mycoplasma InfectionJudy Hickman-Davis1,1 Department of Anesthesiology, University of Alabama at Birmingham, Schools of Medicine and Public Health, Birmingham, AL, USA, 2 Department of Pediatrics, University of Rochester School of Medicine, Rochester, NY, USA, 3 Department of Biostatistics, University of Alabama at Birmingham, Schools of Medicine and Public Health, Birmingham, AL, USA, 4 Department of Anesthesiology, University of Alabama at Birmingham, Schools of Medicine and Public Health, Birmingham, AL, USA; Department of Physiology and Biophysics, University of Alabama at Birmingham, Schools of Medicine and Public Health, Birmingham, AL, USA, 5 Department of Pediatrics, University of Rochester School of Medicine, Rochester, NY, USA; Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY, USA * To whom correspondence should be addressed. E-mail: sadis{at}uab.edu.
Surfactant dysfunction was studied in C57BL/6 (B6), B6.SP-A-/-, and B6.iNOS-/- mice with pulmonary mycoplasma infection (107 CFU). Cell-free bronchoalveolar lavage (BAL) from uninfected B6.SP-A-/- vs. B6 mice had a reduced content of very large aggregates (VLA) and an increase in intermediate large aggregates (ILA), with no difference in total large aggregates (LA = VLA + ILA). However, LA from uninfected B6.SP-A-/- vs. B6 mice contained less protein and were more sensitive to inhibition by serum albumin and lysophosphatidylcholine in pulsating bubble studies in vitro. Infection with M. pulmonis caused significant lung injury and surfactant abnormalities in B6.SP-A-/-, B6.iNOS-/-, and B6 mice at 24, 48, 72 h post infection compared to uninfected mice of the same strain. Analyses of time- pooled data indicated that mycoplasma-infected B6.SP-A-/- and B6.iNOS-/- mice had significantly lower levels of LA and higher protein/phospholipid ratios in BAL compared to infected B6 mice. Infected B6.iNOS-/- vs. B6 mice also had increased minimum surface tensions on the pulsating bubble and decreased levels of surfactant protein (SP)-B in BAL. These results indicate that pulmonary mycoplasma infection in vivo causes lung injury and surfactant abnormalities that are dependent in part on iNOS and SP-A. In addition, SP-A-deficiency modifies surfactant aggregate content and lowers the inhibition resistance of LA surfactant in vitro compared to congenic normal mice.
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