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Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes
Cyclic AMP (cAMP) regulates many biological processes and cellular functions. The importance of spatially localized intracellular gradients of cAMP is increasingly appreciated. Previous work in macrophages has shown that cAMP is produced during phagocytosis and that elevated cAMP levels suppress hos...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978719/ https://www.ncbi.nlm.nih.gov/pubmed/21085604 http://dx.doi.org/10.1371/journal.pone.0013962 |
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author | Ballinger, Megan N. Welliver, Timothy Straight, Samuel Peters-Golden, Marc Swanson, Joel A. |
author_facet | Ballinger, Megan N. Welliver, Timothy Straight, Samuel Peters-Golden, Marc Swanson, Joel A. |
author_sort | Ballinger, Megan N. |
collection | PubMed |
description | Cyclic AMP (cAMP) regulates many biological processes and cellular functions. The importance of spatially localized intracellular gradients of cAMP is increasingly appreciated. Previous work in macrophages has shown that cAMP is produced during phagocytosis and that elevated cAMP levels suppress host defense functions, including generation of proinflammatory mediators, phagocytosis and killing. However, the spatial and kinetic characteristics of cAMP generation in phagocytosing macrophages have yet to be examined. Using a Förster resonance energy transfer (FRET)-based cAMP biosensor, we measured the generation of cAMP in live macrophages. We detected no difference in bulk intracellular cAMP levels between resting cells and cells actively phagocytosing IgG-opsonized particles. However, analysis with the biosensor revealed a rapid decrease in FRET signal corresponding to a transient burst of cAMP production localized to the forming phagosome. cAMP levels returned to baseline after the particle was internalized. These studies indicate that localized increases in cAMP accompany phagosome formation and provide a framework for a more complete understanding of how cAMP regulates macrophage host defense functions. |
format | Text |
id | pubmed-2978719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29787192010-11-17 Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes Ballinger, Megan N. Welliver, Timothy Straight, Samuel Peters-Golden, Marc Swanson, Joel A. PLoS One Research Article Cyclic AMP (cAMP) regulates many biological processes and cellular functions. The importance of spatially localized intracellular gradients of cAMP is increasingly appreciated. Previous work in macrophages has shown that cAMP is produced during phagocytosis and that elevated cAMP levels suppress host defense functions, including generation of proinflammatory mediators, phagocytosis and killing. However, the spatial and kinetic characteristics of cAMP generation in phagocytosing macrophages have yet to be examined. Using a Förster resonance energy transfer (FRET)-based cAMP biosensor, we measured the generation of cAMP in live macrophages. We detected no difference in bulk intracellular cAMP levels between resting cells and cells actively phagocytosing IgG-opsonized particles. However, analysis with the biosensor revealed a rapid decrease in FRET signal corresponding to a transient burst of cAMP production localized to the forming phagosome. cAMP levels returned to baseline after the particle was internalized. These studies indicate that localized increases in cAMP accompany phagosome formation and provide a framework for a more complete understanding of how cAMP regulates macrophage host defense functions. Public Library of Science 2010-11-11 /pmc/articles/PMC2978719/ /pubmed/21085604 http://dx.doi.org/10.1371/journal.pone.0013962 Text en Ballinger et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ballinger, Megan N. Welliver, Timothy Straight, Samuel Peters-Golden, Marc Swanson, Joel A. Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes |
title | Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes |
title_full | Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes |
title_fullStr | Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes |
title_full_unstemmed | Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes |
title_short | Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes |
title_sort | transient increase in cyclic amp localized to macrophage phagosomes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978719/ https://www.ncbi.nlm.nih.gov/pubmed/21085604 http://dx.doi.org/10.1371/journal.pone.0013962 |
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