| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Respiratory Medicine Unit, Department of Medicine (RIE), Rayne Laboratory, The University of Edinburgh Medical School, Edinburgh, U.K.
Regulation of macrophage capacity to remove apoptotic cells may control the balance of apoptotic and necrotic leukocytes at inflamed foci and the extent of leukocyte-mediated tissue damage. Although the molecules involved in the phagocytic process are beginning to be defined, little is known about the underlying regulatory and signaling mechanisms controlling this process. In this paper, we have investigated the effects of treatment of human monocyte-derived macrophages with PGs and other agents that elevate intracellular cAMP on phagocytosis. PGE2 and PGD2 specifically reduced the proportion of macrophages that phagocytosed apoptotic cells. Similar results were obtained with the membrane-permeable cAMP analogues dibutyryl-cAMP and 8-bromo-cAMP but not with the cGMP analogue dibutyryl-GMP. Consistent with the observation that phagocytosis was inhibited by cAMP elevation, treatment of monocyte-derived macrophages with PGE2 resulted in rapid, transient increase in levels of intracellular cAMP. These effects were not due to nonspecific inhibition of monocyte-derived macrophage phagocytosis given that ingestion of Ig-opsonized erythrocytes was unaffected. Elevation of cAMP induced morphologic alterations indicative of changes in the adhesive status of the macrophage, including cell rounding and disassembly of structures that represent points of contact with substrate containing actin and talin. These results strongly suggest that rapid activation of cAMP signaling pathways by inflammatory mediators regulates processes that limit tissue injury and that modulation of cAMP levels represents an additional therapeutic target in the control of resolution of inflammation.
This article has been cited by other articles:
|
|
 |
|
  S. Michlewska, I. Dransfield, I. L. Megson, and A. G. Rossi Macrophage phagocytosis of apoptotic neutrophils is critically regulated by the opposing actions of pro-inflammatory and anti-inflammatory agents: key role for TNF-{alpha} FASEB J, March 1, 2009; 23(3): 844 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Rajakariar, J. Newson, E. K. Jackson, P. Sawmynaden, A. Smith, F. Rahman, M. M. Yaqoob, and D. W. Gilroy Nonresolving Inflammation in gp91phox-/- Mice, a Model of Human Chronic Granulomatous Disease, Has Lower Adenosine and Cyclic Adenosine 5'-Monophosphate J. Immunol., March 1, 2009; 182(5): 3262 - 3269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. N. Serhan, R. Yang, K. Martinod, K. Kasuga, P. S. Pillai, T. F. Porter, S. F. Oh, and M. Spite Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions J. Exp. Med., January 16, 2009; 206(1): 15 - 23. [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]
|
|
|
|
 |
|
 P. E. Thomas, M. Peters-Golden, E. S. White, V. J. Thannickal, and B. B. Moore PGE2 inhibition of TGF-beta1-induced myofibroblast differentiation is Smad-independent but involves cell shape and adhesion-dependent signaling Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L417 - L428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Ratcliffe, A. Walding, P. A. Shelton, A. Flaherty, and I. G. Dougall Activation of E-prostanoid4 and E-prostanoid2 receptors inhibits TNF-{alpha} release from human alveolar macrophages Eur. Respir. J., May 1, 2007; 29(5): 986 - 994. [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]
|
|
|
|
|
|
K. Reville, J. K. Crean, S. Vivers, I. Dransfield, and C. Godson Lipoxin A4 Redistributes Myosin IIA and Cdc42 in Macrophages: Implications for Phagocytosis of Apoptotic Leukocytes J. Immunol., February 1, 2006; 176(3): 1878 - 1888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Walters, M. J. Paul-Clark, S. K. McMaster, K. Ito, I. M. Adcock, and J. A. Mitchell Cigarette Smoke Activates Human Monocytes by an Oxidant-AP-1 Signaling Pathway: Implications for Steroid Resistance Mol. Pharmacol., November 1, 2005; 68(5): 1343 - 1353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Koenigsknecht-Talboo and G. E. Landreth Microglial Phagocytosis Induced by Fibrillar {beta}-Amyloid and IgGs Are Differentially Regulated by Proinflammatory Cytokines J. Neurosci., September 7, 2005; 25(36): 8240 - 8249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Martin, L. A. Allan, M. Lickrish, C. Sampson, N. Morrice, and P. R. Clarke Protein Kinase A Regulates Caspase-9 Activation by Apaf-1 Downstream of Cytochrome c J. Biol. Chem., April 15, 2005; 280(15): 15449 - 15455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Maderna, S. Yona, M. Perretti, and C. Godson Modulation of Phagocytosis of Apoptotic Neutrophils by Supernatant from Dexamethasone-Treated Macrophages and Annexin-Derived Peptide Ac2-26 J. Immunol., March 15, 2005; 174(6): 3727 - 3733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. G. de Almeida, L. B. Chiarini, J. P. da Silva, P. M. R. e Silva, M. A. Martins, and R. Linden The cellular prion protein modulates phagocytosis and inflammatory response J. Leukoc. Biol., February 1, 2005; 77(2): 238 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Aronoff, C. Canetti, and M. Peters-Golden Prostaglandin E2 Inhibits Alveolar Macrophage Phagocytosis through an E-Prostanoid 2 Receptor-Mediated Increase in Intracellular Cyclic AMP J. Immunol., July 1, 2004; 173(1): 559 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yamaryo, K. Oishi, H. Yoshimine, Y. Tsuchihashi, K. Matsushima, and T. Nagatake Fourteen-Member Macrolides Promote the Phosphatidylserine Receptor-Dependent Phagocytosis of Apoptotic Neutrophils by Alveolar Macrophages Antimicrob. Agents Chemother., January 1, 2003; 47(1): 48 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mitchell, G. Thomas, K. Harvey, D. Cottell, K. Reville, G. Berlasconi, N. A. Petasis, L. Erwig, A. J. Rees, J. Savill, et al. Lipoxins, Aspirin-Triggered Epi-Lipoxins, Lipoxin Stable Analogues, and the Resolution of Inflammation: Stimulation of Macrophage Phagocytosis of Apoptotic Neutrophils In Vivo J. Am. Soc. Nephrol., October 1, 2002; 13(10): 2497 - 2507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Burzyn, C. C. Jancic, S. Zittermann, M. I. Keller Sarmiento, L. Fainboim, R. E. Rosenstein, and H. E. Chuluyan Decrease in cAMP levels modulates adhesion to fibronectin and immunostimulatory ability of human dendritic cells J. Leukoc. Biol., July 1, 2002; 72(1): 93 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.L.Y. Cheuk, S.B. C. Chew, R.R. Fiscus, and P.Y.D. Wong Cyclooxygenase-2 Regulates Apoptosis in Rat Epididymis Through Prostaglandin D2 Biol Reprod, February 1, 2002; 66(2): 374 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M CUTOLO, A SULLI, C PIZZORNI, B SERIOLO, and R H STRAUB Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis Ann Rheum Dis, August 1, 2001; 60(8): 729 - 735. [Full Text] [PDF]
|
|
|
|
|
|
K. M. Giles, K. Ross, A. G. Rossi, N. A. Hotchin, C. Haslett, and I. Dransfield Glucocorticoid Augmentation of Macrophage Capacity for Phagocytosis of Apoptotic Cells Is Associated with Reduced p130Cas Expression, Loss of Paxillin/pyk2 Phosphorylation, and High Levels of Active Rac J. Immunol., July 15, 2001; 167(2): 976 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Godson, S. Mitchell, K. Harvey, N. A. Petasis, N. Hogg, and H. R. Brady Cutting Edge: Lipoxins Rapidly Stimulate Nonphlogistic Phagocytosis of Apoptotic Neutrophils by Monocyte-Derived Macrophages J. Immunol., February 15, 2000; 164(4): 1663 - 1667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. HASLETT Granulocyte Apoptosis and Its Role in the Resolution and Control of Lung Inflammation Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): S5 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-P. Erwig, S. Gordon, G. M. Walsh, and A. J. Rees Previous Uptake of Apoptotic Neutrophils or Ligation of Integrin Receptors Downmodulates the Ability of Macrophages to Ingest Apoptotic Neutrophils Blood, February 15, 1999; 93(4): 1406 - 1412. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
