title: Differences in the BAL proteome after Klebsiella pneumoniae infection in wild type and SP-A-/- mice.
abstract: BACKGROUND
  Surfactant protein-A (SP-A) has been shown to play a variety of roles related to lung host defense function. Mice lacking SP-A are more susceptible to infection than wild type C57BL/6 mice. We studied bronchoalveolar lavage (BAL) protein expression in wild type and SP-A-/- mice infected with Klebsiella pneumoniae by 2D-DIGE.
  
  
  METHODS
  Mice were infected intratracheally with K. pneumoniae and after 4 and 24 hours they were subject to BAL. Cell-free BAL was analyzed by 2D-DIGE on two-dimensional gels with pH ranges of 4-7 and 7-11. Under baseline conditions and at 4 and 24 hr post-infection BAL was compared between untreated and infected wild type and SP-A-/- mice. Sixty proteins identified by mass spectrometry were categorized as host defense, redox regulation, and protein metabolism/modification.
  
  
  RESULTS
  We found: 1) ~75% of 32 host defense proteins were lower in uninfected SP-A-/- vs wild type, suggesting increased susceptibility to infection or oxidative injury; 2) At 4 hr post-infection > 2/3 of identified proteins were higher in SP-A-/- than wild type mice, almost the exact opposite of untreated mice; 3) At 24 hr post-infection some proteins continued increasing, but many returned to baseline; 4) In infected wild type mice significant changes occurred in 13 of 60 proteins, with 12 of 13 increasing, vs on 4 significant changes in SP-A-/- mice. Infection response patterns between strains demonstrated both commonalities and differences. In several cases changes between 4 and 24 hr followed different patterns between strains.
  
  
  CONCLUSIONS
  These indicate that SP-A plays a key role in regulating the BAL proteome, functioning indirectly to regulate lung host defense function, possibly via the macrophage. In the absence of SP-A baseline levels of many host defense molecules are lower. However, many of these indirect deficits in SP-A-/- mice are rapidly compensated for during infection, indicating that SP-A also has a direct role on host defense against K. pneumoniae that may be instrumental in determining clinical course.
authors.affiliation: Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Hershey, PA 17033, USA.|Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Mehboob
authors.initials: M
authors.lastname: Ali
authors.affiliation: Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Hershey, PA 17033, USA.|Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Umstead
authors.affiliation: Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Hershey, PA 17033, USA.|Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Rizwanul
authors.initials: R
authors.lastname: Haque
authors.affiliation: Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Hershey, PA 17033, USA.|Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Mikerov
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Willard M
authors.initials: WM
authors.lastname: Freeman
authors.affiliation: Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Hershey, PA 17033, USA.|Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|Department of Obstetrics and Gynecology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
authors.affiliation: Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Hershey, PA 17033, USA.|Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Phelps