© 1996 American Heart Association, Inc.
Articles |
Complement-Induced Release of Monocyte Chemotactic Protein-1 From Human Smooth Muscle Cells
A Possible Initiating Event in Atherosclerotic Lesion Formation
From the Department of Pathology, University of Cambridge, and the MRC Molecular Immunopathology Unit (R.O., P.L.), MRC Centre, Cambridge, UK.
Correspondence to Dr Med Jan Torzewski, University of Ulm, Internal Medicine II, Department of Cardiology, Robert Koch-Str 8, 89081 Ulm, Germany.
Abstract Increasing evidence suggests that complement activation might represent an important mechanism in early atherogenesis. Thus, complement components, in particular the membrane attack complex (MAC) C5b-9(m), have been isolated from human atherosclerotic lesions. Furthermore, complement activation is known to occur in atherosclerotic lesions induced in experimental animals, and the severity of cholesterol-induced plaques is markedly reduced in complement-deficient animals. During atherogenesis monocytes are recruited into the arterial wall, and a potent chemoattractant for monocytes, monocyte chemotactic protein-1 (MCP-1), is expressed by vascular smooth muscle cells (SMCs). We hypothesized that generation of MACs on SMCs during the activation of complement might lead to the release of MCP-1 and hence to monocyte recruitment. In this study, MACs were generated on human SMCs in vitro by sequential addition of the purified complement components C5b6, C7, C8, and C9. The supernatant of the culture was chemotactic for freshly isolated peripheral blood monocytes in a modified Boyden chamber. The chemotactic activity of the supernatant was abolished by anti–MCP-1 blocking antibodies but not by an isotype-matched antibody against an irrelevant antigen. The release of chemotactic activity was dependent on the dose of MAC formed on SMCs and was demonstrated within 10 minutes of exposure of the cells. The data support the hypothesis that complement-mediated release of MCP-1 from SMCs might be important in the recruitment of monocytes into the developing atherosclerotic lesion and could be an important initiating event in atherogenesis.
Key Words: atherogenesis • complement • smooth muscle cells • monocytes • monocyte chemotactic protein-1
This article has been cited by other articles:
 |
|
 |
|
  G. Wu, W. Hu, A. Shahsafaei, W. Song, M. Dobarro, G. K. Sukhova, R. R. Bronson, G.-p. Shi, R. P. Rother, J. A. Halperin, et al. Complement Regulator CD59 Protects Against Atherosclerosis by Restricting the Formation of Complement Membrane Attack Complex Circ. Res., February 27, 2009; 104(4): 550 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wehner, C. N. Morrell, T. Reynolds, E. R. Rodriguez, and W. M. Baldwin III Antibody and Complement in Transplant Vasculopathy Circ. Res., February 2, 2007; 100(2): 191 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M McMahon, J Grossman, W Chen, and B H Hahn Inflammation and the pathogenesis of atherosclerosis in systemic lupus erythematosus Lupus, November 1, 2006; 15(11_suppl): 59 - 69. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Fosbrink, F. Niculescu, V. Rus, M. L. Shin, and H. Rus C5b-9-induced Endothelial Cell Proliferation and Migration Are Dependent on Akt Inactivation of Forkhead Transcription Factor FOXO1 J. Biol. Chem., July 14, 2006; 281(28): 19009 - 19018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Qin, A. Goldfine, N. Krumrei, L. Grubissich, J. Acosta, M. Chorev, A. P. Hays, and J. A. Halperin Glycation Inactivation of the Complement Regulatory Protein CD59: A Possible Role in the Pathogenesis of the Vascular Complications of Human Diabetes Diabetes, October 1, 2004; 53(10): 2653 - 2661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Bot, J. H. von der Thusen, M. M.P.C. Donners, A. Lucas, M. L. Fekkes, S. C.A. de Jager, J. Kuiper, M. J.A.P. Daemen, T. J.C. van Berkel, S. Heeneman, et al. Serine Protease Inhibitor Serp-1 Strongly Impairs Atherosclerotic Lesion Formation and Induces a Stable Plaque Phenotype in ApoE-/- Mice Circ. Res., September 5, 2003; 93(5): 464 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yilmazer, V. Fenkci, S. Fenkci, O. Aktepe, M. Sonmezer, and G. Kurtay Association of serum complement (C3, C4) and immunoglobulin (IgG, IgM) levels with hormone replacement therapy in healthy post-menopausal women Hum. Reprod., July 1, 2003; 18(7): 1531 - 1535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Kaplan, S. K. O'Neill, T. Koreny, M. Czipri, and A. Finnegan Development of Inflammation in Proteoglycan-Induced Arthritis Is Dependent on Fc{gamma}R Regulation of the Cytokine/Chemokine Environment J. Immunol., November 15, 2002; 169(10): 5851 - 5859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. P. Zwaka, D. Manolov, C. Ozdemir, N. Marx, Z. Kaya, M. Kochs, M. Hoher, V. Hombach, and J. Torzewski Complement and Dilated Cardiomyopathy: A Role of Sublytic Terminal Complement Complex-Induced Tumor Necrosis Factor-{alpha} Synthesis in Cardiac Myocytes Am. J. Pathol., August 1, 2002; 161(2): 449 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Viedt, J. Vogel, T. Athanasiou, W. Shen, S. R. Orth, W. Kubler, and J. Kreuzer Monocyte Chemoattractant Protein-1 Induces Proliferation and Interleukin-6 Production in Human Smooth Muscle Cells by Differential Activation of Nuclear Factor-{kappa}B and Activator Protein-1 Arterioscler Thromb Vasc Biol, June 1, 2002; 22(6): 914 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Hansson Immune Mechanisms in Atherosclerosis Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 1876 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Torzewski, C. Rist, R. F. Mortensen, T. P. Zwaka, M. Bienek, J. Waltenberger, W. Koenig, G. Schmitz, V. Hombach, and J. Torzewski C-Reactive Protein in the Arterial Intima : Role of C-Reactive Protein Receptor-Dependent Monocyte Recruitment in Atherogenesis Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2094 - 2099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Acosta, J. Hettinga, R. Fluckiger, N. Krumrei, A. Goldfine, L. Angarita, and J. Halperin Molecular basis for a link between complement and the vascular complications of diabetes PNAS, May 9, 2000; 97(10): 5450 - 5455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Klouche, S. Rose-John, W. Schmiedt, and S. Bhakdi Enzymatically Degraded, Nonoxidized LDL Induces Human Vascular Smooth Muscle Cell Activation, Foam Cell Transformation, and Proliferation Circulation, April 18, 2000; 101(15): 1799 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Collard, A. Agah, W. Reenstra, J. Buras, and G. L. Stahl Endothelial Nuclear Factor-{kappa}B Translocation and Vascular Cell Adhesion Molecule-1 Induction by Complement : Inhibition With Anti-Human C5 Therapy or cGMP Analogues Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2623 - 2629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Prohaszka, J. Duba, G. Lakos, E. Kiss, L. Varga, L. Janoskuti, A. Csaszar, I. Karadi, K. Nagy, M. Singh, et al. Antibodies against human heat-shock protein (hsp) 60 and mycobacterial hsp65 differ in their antigen specificity and complement-activating ability Int. Immunol., September 1, 1999; 11(9): 1363 - 1370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Schmiedt, R. Kinscherf, H.-P. Deigner, H. Kamencic, O. Nauen, J. Kilo, H. Oelert, J. Metz, and S. Bhakdi Complement C6 Deficiency Protects Against Diet-Induced Atherosclerosis in Rabbits Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1790 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Torzewski, M. Torzewski, D. E. Bowyer, M. Frohlich, W. Koenig, J. Waltenberger, C. Fitzsimmons, and V. Hombach C-Reactive Protein Frequently Colocalizes With the Terminal Complement Complex in the Intima of Early Atherosclerotic Lesions of Human Coronary Arteries Arterioscler Thromb Vasc Biol, September 1, 1998; 18(9): 1386 - 1392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Torzewski, J. Torzewski, D. E. Bowyer, J. Waltenberger, C. Fitzsimmons, V. Hombach, and H. E. Gabbert Immunohistochemical Colocalization of the Terminal Complex of Human Complement and Smooth Muscle Cell {alpha}-Actin in Early Atherosclerotic Lesions Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2448 - 2452. [Abstract] [Full Text]
|
|