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Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2

BACKGROUND: Neonates and young infants manifest increased susceptibility to bacterial, viral and fungal lung infections. Previous work has identified a role for eicosanoids in mediating host defense functions of macrophages. This study examines the relationship between alveolar macrophage (AM) host...

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Autores principales: Ballinger, Megan N, Peters-Golden, Marc, Moore, Bethany B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287971/
https://www.ncbi.nlm.nih.gov/pubmed/22141755
http://dx.doi.org/10.1186/1465-9921-12-155
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author Ballinger, Megan N
Peters-Golden, Marc
Moore, Bethany B
author_facet Ballinger, Megan N
Peters-Golden, Marc
Moore, Bethany B
author_sort Ballinger, Megan N
collection PubMed
description BACKGROUND: Neonates and young infants manifest increased susceptibility to bacterial, viral and fungal lung infections. Previous work has identified a role for eicosanoids in mediating host defense functions of macrophages. This study examines the relationship between alveolar macrophage (AM) host defense and production of lipid mediators during the neonatal period compared to adult AMs. METHODS: AMs were harvested from young (day 7 and day 14) and adult (~10 week) rats. The functionality of these cells was assessed by examining their ability to phagocytose opsonized targets, produce cytokines, eicosanoids and intracellular cAMP measured by enzyme immunoassays, and gene expression of proteins, enzymes and receptors essential for eicosanoid generation and phagocytosis measured by real time RT-PCR. RESULTS: AMs from young animals (day 7 and 14) were defective in their ability to phagocytose opsonized targets and produce tumor necrosis factor (TNF)- α. In addition, young AMs produce more prostaglandin (PG) E(2), a suppressor of host defense, and less leukotriene (LT) B(4), a promoter of host defense. Young AMs express higher levels of enzymes responsible for the production of PGE(2 )and LTB(4); however, there was no change in the expression of E prostanoid (EP) receptors or LT receptors. Despite the similar EP profiles, young AMs are more responsive to PGE(2 )as evidenced by their increased production of the important second messenger, cyclic AMP. In addition, young AMs express higher levels of PDE3B and lower levels of PDE4C compared to adult AMs. However, even though the young AMs produced a skewed eicosanoid profile, neither the inhibition of PGE(2 )by aspirin nor the addition of exogenous LTB(4 )rescued the defective opsonized phagocytosis. Examination of a receptor responsible for mediating opsonized phagocytosis showed a significant decrease in the gene expression levels of the Fcgamma receptor in young (day 7) AMs compared to adult AMs. CONCLUSION: These results suggest that elevated production of PGE(2 )and decreased production of LTB(4 )do not contribute to impaired opsonized macrophage phagocytosis and highlight an important difference between young and adult AMs.
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spelling pubmed-32879712012-02-28 Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2 Ballinger, Megan N Peters-Golden, Marc Moore, Bethany B Respir Res Research BACKGROUND: Neonates and young infants manifest increased susceptibility to bacterial, viral and fungal lung infections. Previous work has identified a role for eicosanoids in mediating host defense functions of macrophages. This study examines the relationship between alveolar macrophage (AM) host defense and production of lipid mediators during the neonatal period compared to adult AMs. METHODS: AMs were harvested from young (day 7 and day 14) and adult (~10 week) rats. The functionality of these cells was assessed by examining their ability to phagocytose opsonized targets, produce cytokines, eicosanoids and intracellular cAMP measured by enzyme immunoassays, and gene expression of proteins, enzymes and receptors essential for eicosanoid generation and phagocytosis measured by real time RT-PCR. RESULTS: AMs from young animals (day 7 and 14) were defective in their ability to phagocytose opsonized targets and produce tumor necrosis factor (TNF)- α. In addition, young AMs produce more prostaglandin (PG) E(2), a suppressor of host defense, and less leukotriene (LT) B(4), a promoter of host defense. Young AMs express higher levels of enzymes responsible for the production of PGE(2 )and LTB(4); however, there was no change in the expression of E prostanoid (EP) receptors or LT receptors. Despite the similar EP profiles, young AMs are more responsive to PGE(2 )as evidenced by their increased production of the important second messenger, cyclic AMP. In addition, young AMs express higher levels of PDE3B and lower levels of PDE4C compared to adult AMs. However, even though the young AMs produced a skewed eicosanoid profile, neither the inhibition of PGE(2 )by aspirin nor the addition of exogenous LTB(4 )rescued the defective opsonized phagocytosis. Examination of a receptor responsible for mediating opsonized phagocytosis showed a significant decrease in the gene expression levels of the Fcgamma receptor in young (day 7) AMs compared to adult AMs. CONCLUSION: These results suggest that elevated production of PGE(2 )and decreased production of LTB(4 )do not contribute to impaired opsonized macrophage phagocytosis and highlight an important difference between young and adult AMs. BioMed Central 2011 2011-12-05 /pmc/articles/PMC3287971/ /pubmed/22141755 http://dx.doi.org/10.1186/1465-9921-12-155 Text en Copyright ©2011 Ballinger et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Research
Ballinger, Megan N
Peters-Golden, Marc
Moore, Bethany B
Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2
title Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2
title_full Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2
title_fullStr Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2
title_full_unstemmed Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2
title_short Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2
title_sort impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin e2
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287971/
https://www.ncbi.nlm.nih.gov/pubmed/22141755
http://dx.doi.org/10.1186/1465-9921-12-155
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