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...

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Main Authors: Megan N Ballinger, Timothy Welliver, Samuel Straight, Marc Peters-Golden, Joel A Swanson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-11-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2978719?pdf=render
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author Megan N Ballinger
Timothy Welliver
Samuel Straight
Marc Peters-Golden
Joel A Swanson
author_facet Megan N Ballinger
Timothy Welliver
Samuel Straight
Marc Peters-Golden
Joel A Swanson
author_sort Megan N Ballinger
collection DOAJ
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.
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spelling doaj.art-7c60f6b5860d45618ff55777de2c3abd2022-12-21T17:50:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-11-01511e1396210.1371/journal.pone.0013962Transient increase in cyclic AMP localized to macrophage phagosomes.Megan N BallingerTimothy WelliverSamuel StraightMarc Peters-GoldenJoel A SwansonCyclic 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.http://europepmc.org/articles/PMC2978719?pdf=render
spellingShingle Megan N Ballinger
Timothy Welliver
Samuel Straight
Marc Peters-Golden
Joel A Swanson
Transient increase in cyclic AMP localized to macrophage phagosomes.
PLoS ONE
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
url http://europepmc.org/articles/PMC2978719?pdf=render
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AT samuelstraight transientincreaseincyclicamplocalizedtomacrophagephagosomes
AT marcpetersgolden transientincreaseincyclicamplocalizedtomacrophagephagosomes
AT joelaswanson transientincreaseincyclicamplocalizedtomacrophagephagosomes