| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106;
Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131; and
Department of Medicine, Washington University, St. Louis, MO 63110
Decay-accelerating factor (DAF or CD55) and membrane cofactor protein (MCP or CD46) function intrinsically in the membranes of self cells to prevent activation of autologous complement on their surfaces. How these two regulatory proteins cooperate on self-cell surfaces to inhibit autologous complement attack is unknown. In this study, a GPI-anchored form of MCP was generated. The ability of this recombinant protein and that of naturally GPI-anchored DAF to incorporate into cell membranes then was exploited to examine the combined functions of DAF and MCP in regulating complement intermediates assembled from purified alternative pathway components on rabbit erythrocytes. Quantitative studies with complement-coated rabbit erythrocyte intermediates constituted with each protein individually or the two proteins together demonstrated that DAF and MCP synergize the actions of each other in preventing C3b deposition on the cell surface. Further analyses showed that MCP’s ability to catalyze the factor I-mediated cleavage of cell-bound C3b is inhibited in the presence of factors B and D and is restored when DAF is incorporated into the cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two proteins individually, and DAF is required for MCP to catalyze the cleavage of cell-bound C3b in the presence of excess factors B and D. These data are relevant to xenotransplantation, pharmacological inhibition of complement in inflammatory diseases, and evasion of tumor cells from humoral immune responses.
This article has been cited by other articles:
|
|
 |
|
  C. J. Fang, V. Fremeaux-Bacchi, M. K. Liszewski, G. Pianetti, M. Noris, T. H. J. Goodship, and J. P. Atkinson Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome Blood, January 15, 2008; 111(2): 624 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Buettner, M. Huang, T. Gritsko, J. Karras, S. Enkemann, T. Mesa, S. Nam, H. Yu, and R. Jove Activated Signal Transducers and Activators of Transcription 3 Signaling Induces CD46 Expression and Protects Human Cancer Cells from Complement-Dependent Cytotoxicity Mol. Cancer Res., August 1, 2007; 5(8): 823 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Harris, D. M. Pettigrew, S. M. Lea, and B. P. Morgan Decay-Accelerating Factor Must Bind Both Components of the Complement Alternative Pathway C3 Convertase to Mediate Efficient Decay J. Immunol., January 1, 2007; 178(1): 352 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Liszewski, M. K. Leung, R. Hauhart, R. M. L. Buller, P. Bertram, X. Wang, A. M. Rosengard, G. J. Kotwal, and J. P. Atkinson Structure and Regulatory Profile of the Monkeypox Inhibitor of Complement: Comparison to Homologs in Vaccinia and Variola and Evidence for Dimer Formation J. Immunol., March 15, 2006; 176(6): 3725 - 3734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lin, D. Spencer, D. A. Hatala, A. D. Levine, and M. E. Medof Decay-Accelerating Factor Deficiency Increases Susceptibility to Dextran Sulfate Sodium-Induced Colitis: Role for Complement in Inflammatory Bowel Disease J. Immunol., March 15, 2004; 172(6): 3836 - 3841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lin, D. J. Salant, H. Meyerson, S. Emancipator, B. P. Morgan, and M. E. Medof Respective Roles of Decay-Accelerating Factor and CD59 in Circumventing Glomerular Injury in Acute Nephrotoxic Serum Nephritis J. Immunol., February 15, 2004; 172(4): 2636 - 2642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Gill, M. Koomey, J. G. Cannon, and J. P. Atkinson Down-regulation of CD46 by Piliated Neisseria gonorrhoeae J. Exp. Med., November 3, 2003; 198(9): 1313 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Uhrinova, F. Lin, G. Ball, K. Bromek, D. Uhrin, M. E. Medof, and P. N. Barlow Solution structure of a functionally active fragment of decay-accelerating factor PNAS, April 15, 2003; 100(8): 4718 - 4723. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
