Differences in the BAL proteome after Klebsiella pneumoniae infection in wild type and SP-A-/- mice

Proteome Science

Research

Willard M Freeman¹  Rizwanul Haque²  Todd M Umstead²  David S Phelps²  Anatoly N Mikerov²  Mehboob Ali²  Joanna Floros³ 

[1] Department of Pharmacology, The Pennsylvania State University College of Medicine, 17033, Hershey, PA, USA;Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, 17033, Hershey, PA, USA;Department of Pediatrics, The Pennsylvania State University College of Medicine, 17033, Hershey, PA, USA;Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, 17033, Hershey, PA, USA;Department of Pediatrics, The Pennsylvania State University College of Medicine, 17033, Hershey, PA, USA;Department of Obstetrics and Gynecology, The Pennsylvania State University College of Medicine, USA, 17033, Hershey, PA;

关键词: Wild Type Mouse;    Host Defense;    Host Defense Function;    Infected Wild Type;    Negative Acute Phase Protein;   

DOI  :  10.1186/1477-5956-8-34

 received in 2010-04-07, accepted in 2010-06-17,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundSurfactant 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.MethodsMice 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.ResultsWe 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.ConclusionsThese 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.

【 授权许可】

Unknown   
© Ali et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.