| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612
Physiological cell death is a process the purpose of which is the elimination of functionally inappropriate cells in a manner that does not elicit an inflammatory response. We have shown previously that the ability of apoptotic corpses to be recognized by macrophages and to modulate the proinflammatory responses of those cells represents paradoxically a gain-of-function acquired during the physiological cell death process. Cells that die pathologically (that is, necrotic vs apoptotic corpses) also are recognized by macrophages but do not down-regulate macrophage inflammatory responses; the recognition of these two classes of native dying cells occurs via distinct and noncompeting mechanisms. We have examined the apoptotic modulation of proinflammatory cytokine gene transcription in macrophages (by real-time RT-PCR analysis) and the corresponding modulation of transcriptional activators (by transcriptional reporter analyses). Our data demonstrate that apoptotic cells target the proinflammatory transcriptional machinery of macrophages with which they interact, without apparent effect on proximal steps of Toll-like receptor signaling. The modulatory activity of the corpse is manifest as an immediate-early inhibition of proinflammatory cytokine gene transcription, and is exerted directly upon binding to the macrophage, independent of subsequent engulfment and soluble factor involvement. Recognition and inflammatory modulation represent key elements of an innate immune response that discriminates live from effete cells, and without regard to self.
This article has been cited by other articles:
|
|
 |
|
  N. Tibrewal, Y. Wu, V. D'mello, R. Akakura, T. C. George, B. Varnum, and R. B. Birge Autophosphorylation Docking Site Tyr-867 in Mer Receptor Tyrosine Kinase Allows for Dissociation of Multiple Signaling Pathways for Phagocytosis of Apoptotic Cells and Down-modulation of Lipopolysaccharide-inducible NF-{kappa}B Transcriptional Activation J. Biol. Chem., February 8, 2008; 283(6): 3618 - 3627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Johann, A. Weigert, W. Eberhardt, A.-M. Kuhn, V. Barra, A. von Knethen, J. M. Pfeilschifter, and B. Brune Apoptotic Cell-Derived Sphingosine-1-Phosphate Promotes HuR-Dependent Cyclooxygenase-2 mRNA Stabilization and Protein Expression J. Immunol., January 15, 2008; 180(2): 1239 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. A. Swisher, U. Khatri, and G. M. Feldman Annexin A2 is a soluble mediator of macrophage activation J. Leukoc. Biol., November 1, 2007; 82(5): 1174 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Weigert, N. Tzieply, A. von Knethen, A. M. Johann, H. Schmidt, G. Geisslinger, and B. Brune Tumor Cell Apoptosis Polarizes Macrophages Role of Sphingosine-1-Phosphate Mol. Biol. Cell, October 1, 2007; 18(10): 3810 - 3819. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-P. Erwig and P. M. Henson Immunological Consequences of Apoptotic Cell Phagocytosis Am. J. Pathol., July 1, 2007; 171(1): 2 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Arnold, A. Henry, F. Poron, Y. Baba-Amer, N. van Rooijen, A. Plonquet, R. K. Gherardi, and B. Chazaud Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis J. Exp. Med., May 14, 2007; 204(5): 1057 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-C. Hsu, S.-Y. Chiang, C.-Y. Huang, G. J. Tsay, C.-W. Yang, C.-N. Huang, and B.-S. Tzang Beneficial Effects of Treatment with Transglutaminase Inhibitor Cystamine on Macrophage Response in NZB/W F1 Mice Experimental Biology and Medicine, February 1, 2007; 232(2): 195 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Sen, M. A. Wallet, Z. Yi, Y. Huang, M. Henderson, C. E. Mathews, H. S. Earp, G. Matsushima, A. S. Baldwin Jr, and R. M. Tisch Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-{kappa}B activation in dendritic cells Blood, January 15, 2007; 109(2): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Levine, R. Subang, S. H. Nasr, S. Fournier, G. Lajoie, J. Wither, and J. Rauch Immunization with an Apoptotic Cell-Binding Protein Recapitulates the Nephritis and Sequential Autoantibody Emergence of Systemic Lupus Erythematosus J. Immunol., November 1, 2006; 177(9): 6504 - 6516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lucas, L. M. Stuart, A. Zhang, K. Hodivala-Dilke, M. Febbraio, R. Silverstein, J. Savill, and A. Lacy-Hulbert Requirements for Apoptotic Cell Contact in Regulation of Macrophage Responses J. Immunol., September 15, 2006; 177(6): 4047 - 4054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cvetanovic, J. E. Mitchell, V. Patel, B. S. Avner, Y. Su, P. T. van der Saag, P. L. Witte, S. Fiore, J. S. Levine, and D. S. Ucker Specific Recognition of Apoptotic Cells Reveals a Ubiquitous and Unconventional Innate Immunity J. Biol. Chem., July 21, 2006; 281(29): 20055 - 20067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Mitchell, M. Cvetanovic, N. Tibrewal, V. Patel, O. R. Colamonici, M. O. Li, R. A. Flavell, J. S. Levine, R. B. Birge, and D. S. Ucker The Presumptive Phosphatidylserine Receptor Is Dispensable for Innate Anti-inflammatory Recognition and Clearance of Apoptotic Cells J. Biol. Chem., March 3, 2006; 281(9): 5718 - 5725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Patel, A. Longacre, K. Hsiao, H. Fan, F. Meng, J. E. Mitchell, J. Rauch, D. S. Ucker, and J. S. Levine Apoptotic Cells, at All Stages of the Death Process, Trigger Characteristic Signaling Events That Are Divergent from and Dominant over Those Triggered by Necrotic Cells: IMPLICATIONS FOR THE DELAYED CLEARANCE MODEL OF AUTOIMMUNITY J. Biol. Chem., February 24, 2006; 281(8): 4663 - 4670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fan, V. A. Patel, A. Longacre, and J. S. Levine Abnormal regulation of the cytoskeletal regulator Rho typifies macrophages of the major murine models of spontaneous autoimmunity J. Leukoc. Biol., January 1, 2006; 79(1): 155 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Bertho, H. Adamski, L. Toujas, M. Debove, J. Davoust, and V. Quillien Efficient migration of dendritic cells toward lymph node chemokines and induction of TH1 responses require maturation stimulus and apoptotic cell interaction Blood, September 1, 2005; 106(5): 1734 - 1741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Falasca, V. Iadevaia, F. Ciccosanti, G. Melino, A. Serafino, and M. Piacentini Transglutaminase Type II Is a Key Element in the Regulation of the Anti-Inflammatory Response Elicited by Apoptotic Cell Engulfment J. Immunol., June 1, 2005; 174(11): 7330 - 7340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takahashi, C. D.P. Rochford, and H. Neumann Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2 J. Exp. Med., February 22, 2005; 201(4): 647 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Devitt, K. G. Parker, C. A. Ogden, C. Oldreive, M. F. Clay, L. A. Melville, C. O. Bellamy, A. Lacy-Hulbert, S. C. Gangloff, S. M. Goyert, et al. Persistence of apoptotic cells without autoimmune disease or inflammation in CD14-/- mice J. Cell Biol., December 20, 2004; 167(6): 1161 - 1170. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
