| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1H for Cell-Bound C3b1From the Departments of Medicine, Harvard Medical School and the Robert B. Brigham Division of the Affiliated Hospitals Center, Inc., Boston, Massachusetts 02120
Abstract
The relative affinity of B and 
1H for particle-bound C3b is influenced by the relative abundance of cell surface sialic acid moieties and determines whether or not the particle has the capacity to activate the human alternative complement pathway. The effect of membrane sialic acid on the binding of B and 1H to particle bound C3b was determined with radiolabeled proteins and a technique for separating bound from free ligand by centrifugation of the particles through an oil/aqueous interphase. The affinity constants at equilibrium and the effective number of C3b binding sites for B and 1H on the particles were determined by Scatchard analysis of the binding data. The sheep erythrocyte (Es) served as a nonactivating particle, whereas the activating particles included Es from which 80% of the membrane sialic acid residues had been removed by sialidase or 80 to 85% had been converted to heptulosonic acid by NaIO4 and NaBH4 treatment and zymosan particles that lack sialic acid. The affinity constants at equilibrium for C3b on EsC3b were 1 x 107 M-1 for 1H and 2.1 x 106 M-1 for B, in the presence of 5 mM Mg++, indicating an approximately 5-fold greater affinity of 1H for the binding sites that were present in approximately equal numbers for the two ligands as determined by Scatchard analysis. The affinity of B at equilibrium for C3b bound to sialic acid-deficient sheep erythrocytes and to zymosan was the same as that for C3b on Es, and the calculated number of effective binding sites for B agreed with the number of sites estimated by the prior uptake of radiolabeled C3b. In contrast, the number of C3b binding sites with an affinity for 1H of approximately 107 M-1 on sialic acid-deficient EsC3b or ZyC3b was only 
to 
the number interacting with B. The presence of additional binding sites for 1H with an affinity so low that they were not revealed by the Scatchard analysis because of the dominant effect of the high affinity sites was determined in competitive binding studies between B and 1H for C3b on sialic acid-deficient surfaces. The affinity constant of 1H for these sialic acid independent C3b sites is approximately 7 x 105 M-1, a K1H at least 10-fold less than that of the sialic acid-dependent high affinity C3b sites. The relative inefficiency of 1H in competing with 125I-B for uptake by C3b on the sialic acid-deficient erythrocytes correlated with the decreased capacity of 1H to decay-dissociate C3b,Bb from such particles. Thus a deficiency of sialic acid diminishes the number of high affinity C3b sites for 1H and creates an activating particle on which binding of B by C3b is favored relative to 1H and decay-dissociation of C3b,Bb by 1H is impaired.
Footnotes
1 Supported by Grants AI-07722, AM-05577, and RR-05669 from the National Institutes of Health.
2 Fellow of the Delegation Generale a la Recherche Scientifique et Technique, D.G.R.S.T., France.
3 Research Career Development Awardee (K04 AI-00245) from the National Institutes of Health.
This article has been cited by other articles:
|
|
 |
|
  L. A. Lewis, S. Ram, A. Prasad, S. Gulati, S. Getzlaff, A. M. Blom, U. Vogel, and P. A. Rice Defining Targets for Complement Components C4b and C3b on the Pathogenic Neisseriae Infect. Immun., January 1, 2008; 76(1): 339 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. E. Prosser, S. Johnson, P. Roversi, A. P. Herbert, B. S. Blaum, J. Tyrrell, T. A. Jowitt, S. J. Clark, E. Tarelli, D. Uhrin, et al. Structural basis for complement factor H linked age-related macular degeneration J. Exp. Med., October 1, 2007; 204(10): 2277 - 2283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Fenaille, M. Le Mignon, C. Groseil, C. Ramon, S. Riande, L. Siret, and N. Bihoreau Site-specific N-glycan characterization of human complement factor H Glycobiology, September 1, 2007; 17(9): 932 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. MERI Loss of Self-Control in the Complement System and Innate Autoreactivity Ann. N.Y. Acad. Sci., August 1, 2007; 1109(1): 93 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Koch, C. E. Jordan, and J. L. Platt Complement-Dependent Control of Teratoma Formation by Embryonic Stem Cells J. Immunol., October 1, 2006; 177(7): 4803 - 4809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Clark, V. A. Higman, B. Mulloy, S. J. Perkins, S. M. Lea, R. B. Sim, and A. J. Day His-384 Allotypic Variant of Factor H Associated with Age-related Macular Degeneration Has Different Heparin Binding Properties from the Non-disease-associated Form J. Biol. Chem., August 25, 2006; 281(34): 24713 - 24720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. McRae, T. G. Duthy, K. M. Griggs, R. J. Ormsby, P. J. Cowan, B. A. Cromer, W. J. McKinstry, M. W. Parker, B. F. Murphy, and D. L. Gordon Human Factor H-Related Protein 5 Has Cofactor Activity, Inhibits C3 Convertase Activity, Binds Heparin and C-Reactive Protein, and Associates with Lipoprotein J. Immunol., May 15, 2005; 174(10): 6250 - 6256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-A. Dragon-Durey, C. Loirat, S. Cloarec, M.-A. Macher, J. Blouin, H. Nivet, L. Weiss, W. H. Fridman, and V. Fremeaux-Bacchi Anti-Factor H Autoantibodies Associated with Atypical Hemolytic Uremic Syndrome J. Am. Soc. Nephrol., February 1, 2005; 16(2): 555 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-A. Dragon-Durey, V. Fremeaux-Bacchi, C. Loirat, J. Blouin, P. Niaudet, G. Deschenes, P. Coppo, W. Herman Fridman, and L. Weiss Heterozygous and Homozygous Factor H Deficiencies Associated with Hemolytic Uremic Syndrome or Membranoproliferative Glomerulonephritis: Report and Genetic Analysis of 16 Cases J. Am. Soc. Nephrol., March 1, 2004; 15(3): 787 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Drysdale, A. Bourgogne, S. G. Hilsenbeck, and T. M. Koehler atxA Controls Bacillus anthracis Capsule Synthesis via acpA and a Newly Discovered Regulator, acpB J. Bacteriol., January 15, 2004; 186(2): 307 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Caprioli, F. Castelletti, S. Bucchioni, P. Bettinaglio, E. Bresin, G. Pianetti, S. Gamba, S. Brioschi, E. Daina, G. Remuzzi, et al. Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease Hum. Mol. Genet., December 15, 2003; 12(24): 3385 - 3395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hellwage, T. S. Jokiranta, M. A. Friese, T. U. Wolk, E. Kampen, P. F. Zipfel, and S. Meri Complement C3b/C3d and Cell Surface Polyanions Are Recognized by Overlapping Binding Sites on the Most Carboxyl-Terminal Domain of Complement Factor H J. Immunol., December 15, 2002; 169(12): 6935 - 6944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Pangburn Cutting Edge: Localization of the Host Recognition Functions of Complement Factor H at the Carboxyl-Terminal: Implications for Hemolytic Uremic Syndrome J. Immunol., November 1, 2002; 169(9): 4702 - 4706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jain, A. Karadag, B. Fohr, L. W. Fisher, and N. S. Fedarko Three SIBLINGs (Small Integrin-Binding LIgand, N-linked Glycoproteins) Enhance Factor H's Cofactor Activity Enabling MCP-like Cellular Evasion of Complement-mediated Attack J. Biol. Chem., April 12, 2002; 277(16): 13700 - 13708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Moghimi, A. C. Hunter, and J. C. Murray Long-Circulating and Target-Specific Nanoparticles: Theory to Practice Pharmacol. Rev., June 1, 2001; 53(2): 283 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Pangburn, K. L. W. Pangburn, V. Koistinen, S. Meri, and A. K. Sharma Molecular Mechanisms of Target Recognition in an Innate Immune System: Interactions Among Factor H, C3b, and Target in the Alternative Pathway of Human Complement ,2 J. Immunol., May 1, 2000; 164(9): 4742 - 4751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jarva, T. S. Jokiranta, J. Hellwage, P. F. Zipfel, and S. Meri Regulation of Complement Activation by C-Reactive Protein: Targeting the Complement Inhibitory Activity of Factor H by an Interaction with Short Consensus Repeat Domains 7 and 8-11 J. Immunol., October 1, 1999; 163(7): 3957 - 3962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. O'Keefe, G. T. Williams, F. D. Batista, and M. S. Neuberger Deficiency in CD22, a B Cell-specific Inhibitory Receptor, Is Sufficient to Predispose to Development of High Affinity Autoantibodies J. Exp. Med., April 19, 1999; 189(8): 1307 - 1313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sahu, S. N. Isaacs, A. M. Soulika, and J. D. Lambris Interaction of Vaccinia Virus Complement Control Protein with Human Complement Proteins: Factor I-Mediated Degradation of C3b to iC3b1 Inactivates the Alternative Complement Pathway J. Immunol., June 1, 1998; 160(11): 5596 - 5604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Kozel, R. S. MacGill, and K. K. Wall Bivalency Is Required for Anticapsular Monoclonal Antibodies To Optimally Suppress Activation of the Alternative Complement Pathway by the Cryptococcus neoformans Capsule Infect. Immun., April 1, 1998; 66(4): 1547 - 1553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Blackmore, J. Hellwage, T. A. Sadlon, N. Higgs, P. F. Zipfel, H. M. Ward, and D. L. Gordon Identification of the Second Heparin-Binding Domain in Human Complement Factor H J. Immunol., April 1, 1998; 160(7): 3342 - 3348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ram, A. K. Sharma, S. D. Simpson, S. Gulati, D. P. McQuillen, M. K. Pangburn, and P. A. Rice A Novel Sialic Acid Binding Site on Factor H Mediates Serum Resistance of Sialylated Neisseria gonorrhoeae J. Exp. Med., March 2, 1998; 187(5): 743 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kraus, M. E. Medof, and C. Mold Complementary Recognition of Alternative Pathway Activators by Decay-Accelerating Factor and Factor H Infect. Immun., February 1, 1998; 66(2): 399 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-X. Shi, R. Chammas, N. M. Varki, L. Powell, and A. Varki Sialic Acid 9-O-Acetylation on Murine Erythroleukemia Cells Affects Complement Activation, Binding to I-type Lectins, and Tissue Homing J. Biol. Chem., December 6, 1996; 271(49): 31526 - 31532. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
