|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1661-1667
Compstatin Inhibits Complement and Cellular Activation in Whole
Blood in Two Models of Extracorporeal Circulation
Bo Nilsson,
Rolf Larsson,
Jaan Hong,
Graciela Elgue,
Kristina
Nilsson Ekdahl,
Arvind Sahu, and
John D. Lambris
From the Department of Clinical Immunology and Transfusion Medicine,
University Hospital, Uppsala; the Department of Natural Sciences,
University of Kalmar, Sweden; and the Laboratory of Protein Chemistry,
The Department of Pathology and Laboratory Medicine, University of
Pennsylvania, Philadelphia.
Recently, a C3-binding cyclic synthetic peptide (Compstatin) has
been identified that binds to complement component C3 and inhibits
complement activation. Here we have examined the influence of
Compstatin on complement activation and its indirect effects on
cellular responses in whole blood in two models for extracorporeal circulation. Compstatin effectively inhibited the generation of C3a and
sC5b-9 and the binding of C3/ C3 fragments to the polymer surface. As a
result of the inhibition of complement activation, the activation of
polymorphonuclear leukocytes (PMNs; as assessed by the
expression of CD11b) and the binding of these cells
(CD16+) to the polymer surface were almost completely
lost. In contrast, blood cell counts were not affected. Using surface
plasmon resonance technology, we have confirmed that Compstatin exerts
its inhibitory effect on complement activation by binding to native C3.
These data show that complement activation, leading to activation and binding of PMNs to the biomaterial surface, can be abolished by the
addition of Compstatin. The properties of Compstatin make Compstatin a
promising drug for use in extracorporeal circuits to avoid
bioincompatibility reactions, eg, during cardiopulmonary bypass, but
also a favorable precursor peptide for the development of an
anticomplement drug for oral use.
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. W. Hammon
Extracorporeal Circulation: The Response of Humoral and Cellular Elements of Blood to Extracorporeal Circulation
Card. Surg. Adult,
January 1, 2008;
3(2008):
370 - 389.
[Full Text]
|
|
|
|
|
|
|
B. J. C. Janssen, E. F. Halff, J. D. Lambris, and P. Gros
Structure of Compstatin in Complex with Complement Component C3c Reveals a New Mechanism of Complement Inhibition
J. Biol. Chem.,
October 5, 2007;
282(40):
29241 - 29247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. T. Lappegard, M. Fung, G. Bergseth, J. Riesenfeld, J. D. Lambris, V. Videm, and T. E. Mollnes
Effect of complement inhibition and heparin coating on artificial surface-induced leukocyte and platelet activation
Ann. Thorac. Surg.,
March 1, 2004;
77(3):
932 - 941.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Chong, C. R. Hampton, and E. D. Verrier
Microvascular Inflammatory Response in Cardiac Surgery
Seminars in Cardiothoracic and Vascular Anesthesia,
September 1, 2003;
7(3):
333 - 354.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. M. Soulika, D. Morikis, M.-R. Sarrias, M. Roy, L. A. Spruce, A. Sahu, and J. D. Lambris
Studies of Structure-Activity Relations of Complement Inhibitor Compstatin
J. Immunol.,
August 15, 2003;
171(4):
1881 - 1890.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. I-H. Hsu and W. G. Couser
Chronic Progression of Tubulointerstitial Damage in Proteinuric Renal Disease Is Mediated by Complement Activation: A Therapeutic Role for Complement Inhibitors?
J. Am. Soc. Nephrol.,
July 1, 2003;
14(90002):
S186 - 191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. G. Couser
Complement Inhibitors And Glomerulonephritis: Are We There Yet?
J. Am. Soc. Nephrol.,
March 1, 2003;
14(3):
815 - 818.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Menasche and L. H. Edmunds Jr.
Extracorporeal Circulation: The Inflammatory Response
Card. Surg. Adult,
January 1, 2003;
2(2003):
349 - 360.
[Full Text]
|
|
|
|
|
|
|
A. Sahu and J. D. Lambris
Invited commentary
Ann. Thorac. Surg.,
August 1, 2002;
74(2):
362 - 362.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Andersson, K. N. Ekdahl, R. Larsson, U. R. Nilsson, and B. Nilsson
C3 Adsorbed to a Polymer Surface Can Form an Initiating Alternative Pathway Convertase
J. Immunol.,
June 1, 2002;
168(11):
5786 - 5791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Morikis, M. Roy, A. Sahu, A. Troganis, P. A. Jennings, G. C. Tsokos, and J. D. Lambris
The Structural Basis of Compstatin Activity Examined by Structure-Function-based Design of Peptide Analogs and NMR
J. Biol. Chem.,
April 19, 2002;
277(17):
14942 - 14953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Roos, A. J. Nauta, D. Broers, M. C. Faber-Krol, L. A. Trouw, J. W. Drijfhout, and M. R. Daha
Specific Inhibition of the Classical Complement Pathway by C1q-Binding Peptides
J. Immunol.,
December 15, 2001;
167(12):
7052 - 7059.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Fung, P. G. Loubser, A. Undar, M. Mueller, C. Sun, W. N. Sun, W. K. Vaughn, and C. D. Fraser Jr
Inhibition of complement, neutrophil, and platelet activation by an anti-factor D monoclonal antibody in simulated cardiopulmonary bypass circuits
J. Thorac. Cardiovasc. Surg.,
July 1, 2001;
122(1):
113 - 122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sahu, A. M. Soulika, D. Morikis, L. Spruce, W. T. Moore, and J. D. Lambris
Binding Kinetics, Structure-Activity Relationship, and Biotransformation of the Complement Inhibitor Compstatin
J. Immunol.,
September 1, 2000;
165(5):
2491 - 2499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
