|
|
||||||||
CUTTING EDGE |


,


Divisions of
*
Infectious Diseases and
Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109; and
Department of Immunology, Instituto de Ciências Biomédicas-IV, University of São Paulo, São Paulo, Brazil
cAMP has largely inhibitory effects on components of macrophage activation, yet downstream mechanisms involved in these effects remain incompletely defined. Elevation of cAMP in alveolar macrophages (AMs) suppresses Fc
R-mediated phagocytosis. We now report that protein kinase A (PKA) inhibitors (H-89, KT-5720, and myristoylated PKA inhibitory peptide 1422) failed to prevent this suppression in rat AMs. We identified the expression of the alternative cAMP target, exchange protein directly activated by cAMP-1 (Epac-1), in human and rat AMs. Using cAMP analogs that are highly specific for PKA (N6-benzoyladenosine-3',5'-cAMP) or Epac-1 (8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cAMP), we found that activation of Epac-1, but not PKA, dose-dependently suppressed phagocytosis. By contrast, activation of PKA, but not Epac-1, suppressed AM production of leukotriene B4 and TNF-
, whereas stimulation of either PKA or Epac-1 inhibited AM bactericidal activity and H2O2 production. These experiments now identify Epac-1 in primary macrophages, and define differential roles of Epac-1 vs PKA in the inhibitory effects of cAMP.
This article has been cited by other articles:
![]() |
N. El Zein, B. Badran, and E. Sariban VIP differentially activates {beta}2 integrins, CR1, and matrix metalloproteinase-9 in human monocytes through cAMP/PKA, EPAC, and PI-3K signaling pathways via VIP receptor type 1 and FPRL1 J. Leukoc. Biol., April 1, 2008; 83(4): 972 - 981. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Noor, H. Goldfine, D. E. Tucker, S. Suram, L. L. Lenz, S. Akira, S. Uematsu, M. Girotti, J. V. Bonventre, K. Breuel, et al. Activation of Cytosolic Phospholipase A2{alpha} in Resident Peritoneal Macrophages by Listeria monocytogenes Involves Listeriolysin O and TLR2 J. Biol. Chem., February 22, 2008; 283(8): 4744 - 4755. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. J. Xu, J. S. Reichner, B. Mastrofrancesco, W. L. Henry Jr., and J. E. Albina Prostaglandin E2 Suppresses Lipopolysaccharide-Stimulated IFN-{beta} Production J. Immunol., February 15, 2008; 180(4): 2125 - 2131. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. Kassel, T. A. Wyatt, R. A. Panettieri Jr., and M. L. Toews Inhibition of human airway smooth muscle cell proliferation by 2-adrenergic receptors and cAMP is PKA independent: evidence for EPAC involvement Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L131 - L138. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Canetti, C. H. Serezani, R. G. Atrasz, E. S. White, D. M. Aronoff, and M. Peters-Golden Activation of Phosphatase and Tensin Homolog on Chromosome 10 Mediates the Inhibition of Fc{gamma}R Phagocytosis by Prostaglandin E2 in Alveolar Macrophages J. Immunol., December 15, 2007; 179(12): 8350 - 8356. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Hodge, G. Hodge, J. Ahern, H. Jersmann, M. Holmes, and P. N. Reynolds Smoking Alters Alveolar Macrophage Recognition and Phagocytic Ability: Implications in Chronic Obstructive Pulmonary Disease Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 748 - 755. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Chassin, M. W. Hornef, M. Bens, M. Lotz, J.-M. Goujon, S. Vimont, G. Arlet, A. Hertig, E. Rondeau, and A. Vandewalle Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin J. Exp. Med., November 26, 2007; 204(12): 2837 - 2852. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. H. Serezani, J. Chung, M. N. Ballinger, B. B. Moore, D. M. Aronoff, and M. Peters-Golden Prostaglandin E2 Suppresses Bacterial Killing in Alveolar Macrophages by Inhibiting NADPH Oxidase Am. J. Respir. Cell Mol. Biol., November 1, 2007; 37(5): 562 - 570. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Peres, D. M. Aronoff, C. H. Serezani, N. Flamand, L. H. Faccioli, and M. Peters-Golden Specific Leukotriene Receptors Couple to Distinct G Proteins to Effect Stimulation of Alveolar Macrophage Host Defense Functions J. Immunol., October 15, 2007; 179(8): 5454 - 5461. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Chen, B. Perussia, and K. S. Campbell Prostaglandin D2 Suppresses Human NK Cell Function via Signaling through D Prostanoid Receptor J. Immunol., September 1, 2007; 179(5): 2766 - 2773. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. D. Harzenetter, A. R. Novotny, P. Gais, C. A. Molina, F. Altmayr, and B. Holzmann Negative Regulation of TLR Responses by the Neuropeptide CGRP Is Mediated by the Transcriptional Repressor ICER J. Immunol., July 1, 2007; 179(1): 607 - 615. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Majumdar, D. Cruz, N. Asamoah, A. Buxbaum, I. Sohar, P. Lobel, and F. R. Maxfield Activation of Microglia Acidifies Lysosomes and Leads to Degradation of Alzheimer Amyloid Fibrils Mol. Biol. Cell, April 1, 2007; 18(4): 1490 - 1496. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. M. Aronoff, C. M. Peres, C. H. Serezani, M. N. Ballinger, J. K. Carstens, N. Coleman, B. B. Moore, R. S. Peebles, L. H. Faccioli, and M. Peters-Golden Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities J. Immunol., February 1, 2007; 178(3): 1628 - 1634. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Lorenowicz, J. van Gils, M. de Boer, P. L. Hordijk, and M. Fernandez-Borja Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis J. Leukoc. Biol., December 1, 2006; 80(6): 1542 - 1552. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. G. Holz, G. Kang, M. Harbeck, M. W. Roe, and O. G. Chepurny Cell physiology of cAMP sensor Epac J. Physiol., November 15, 2006; 577(1): 5 - 15. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. N. Ballinger, D. M. Aronoff, T. R. McMillan, K. R. Cooke, K. Olkiewicz, G. B. Toews, M. Peters-Golden, and B. B. Moore Critical Role of Prostaglandin E2 Overproduction in Impaired Pulmonary Host Response following Bone Marrow Transplantation J. Immunol., October 15, 2006; 177(8): 5499 - 5508. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Lokshin, T. Raskovalova, X. Huang, L. C. Zacharia, E. K. Jackson, and E. Gorelik Adenosine-mediated inhibition of the cytotoxic activity and cytokine production by activated natural killer cells. Cancer Res., August 1, 2006; 66(15): 7758 - 7765. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Bryn, M. Mahic, J. M. Enserink, F. Schwede, E. M. Aandahl, and K. Tasken The Cyclic AMP-Epac1-Rap1 Pathway Is Dissociated from Regulation of Effector Functions in Monocytes but Acquires Immunoregulatory Function in Mature Macrophages. J. Immunol., June 15, 2006; 176(12): 7361 - 7370. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. T. Branham, L. S. Mayorga, and C. N. Tomes Calcium-induced Acrosomal Exocytosis Requires cAMP Acting through a Protein Kinase A-independent, Epac-mediated Pathway J. Biol. Chem., March 31, 2006; 281(13): 8656 - 8666. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. T. Bender and J. A. Beavo PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyte PNAS, January 10, 2006; 103(2): 460 - 465. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Osawa, H. T. Lee, C. A. Hirshman, D. Xu, and C. W. Emala Lipopolysaccharide-induced sensitization of adenylyl cyclase activity in murine macrophages Am J Physiol Cell Physiol, January 1, 2006; 290(1): C143 - C151. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |