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

<p>Abstract</p> <p>Background</p> <p>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) pro...

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Main Authors: Mikerov Anatoly N, Haque Rizwanul, Umstead Todd M, Ali Mehboob, Freeman Willard M, Floros Joanna, Phelps David S
Format: Article
Language:English
Published: BMC 2010-06-01
Series:Proteome Science
Online Access:http://www.proteomesci.com/content/8/1/34
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author Mikerov Anatoly N
Haque Rizwanul
Umstead Todd M
Ali Mehboob
Freeman Willard M
Floros Joanna
Phelps David S
author_facet Mikerov Anatoly N
Haque Rizwanul
Umstead Todd M
Ali Mehboob
Freeman Willard M
Floros Joanna
Phelps David S
author_sort Mikerov Anatoly N
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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 <it>Klebsiella pneumoniae </it>by 2D-DIGE.</p> <p>Methods</p> <p>Mice were infected intratracheally with <it>K. pneumoniae </it>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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 <it>K. pneumoniae </it>that may be instrumental in determining clinical course.</p>
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spelling doaj.art-f8f25f52bb5748b3a1faf0aa243dec882022-12-22T03:07:40ZengBMCProteome Science1477-59562010-06-01813410.1186/1477-5956-8-34Differences in the BAL proteome after <it>Klebsiella pneumoniae </it>infection in wild type and SP-A-/- miceMikerov Anatoly NHaque RizwanulUmstead Todd MAli MehboobFreeman Willard MFloros JoannaPhelps David S<p>Abstract</p> <p>Background</p> <p>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 <it>Klebsiella pneumoniae </it>by 2D-DIGE.</p> <p>Methods</p> <p>Mice were infected intratracheally with <it>K. pneumoniae </it>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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 <it>K. pneumoniae </it>that may be instrumental in determining clinical course.</p>http://www.proteomesci.com/content/8/1/34
spellingShingle Mikerov Anatoly N
Haque Rizwanul
Umstead Todd M
Ali Mehboob
Freeman Willard M
Floros Joanna
Phelps David S
Differences in the BAL proteome after <it>Klebsiella pneumoniae </it>infection in wild type and SP-A-/- mice
Proteome Science
title Differences in the BAL proteome after <it>Klebsiella pneumoniae </it>infection in wild type and SP-A-/- mice
title_full Differences in the BAL proteome after <it>Klebsiella pneumoniae </it>infection in wild type and SP-A-/- mice
title_fullStr Differences in the BAL proteome after <it>Klebsiella pneumoniae </it>infection in wild type and SP-A-/- mice
title_full_unstemmed Differences in the BAL proteome after <it>Klebsiella pneumoniae </it>infection in wild type and SP-A-/- mice
title_short Differences in the BAL proteome after <it>Klebsiella pneumoniae </it>infection in wild type and SP-A-/- mice
title_sort differences in the bal proteome after it klebsiella pneumoniae it infection in wild type and sp a mice
url http://www.proteomesci.com/content/8/1/34
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