Although the C1q binding proteins are constitutively expressed on resting nonthrombotic endothelium, and gC1q-R in particular has the potential to bind C1q, as well as HK and FXII, the mechanism by which a continuously thrombogenic state of the endothelium is averted is not completely understood. Based on the available data, however, it is postulated that efficient engagement of gC1q-R by its ligands is restricted to conditions where under chemical, physical, or infectious insult, the endothelial cell is converted to a prothrombotic and proinflammatory phenotype leading to upregulation of gC1q-R, the induction of cytokines such as IL-1 or tumor necrosis factor-a (TNFa), and/or expression of cell adhesion molecules (CAMs). Freshly recruited leukocytes, such as macrophages and T cells bound to the cell adhesion molecules, can also release cytokines, which in turn can amplify the process by upregu-lating the expression of C1q binding molecules in a manner that allows efficient binding of ligands. It has been shown that cytokines, such as LPS, interferon-g (IFNg), and TNFg, can upregulate the expression of both cC1q-R and gC1q-R. Thus, modulation of endothelial cell function by soluble and/or immobilized proinflammatory ligands, such as C1q or HK, especially at sites of inflammatory and vascular lesions, may contribute significantly to the development of thrombosis and exacerbation of the inflammatory process.
Andrews, B. S., Shadforth, M., Cunningham, P., and Davis, J. S. IV (1981). Demonstration of a C1q receptor on the surface of human endothelial cells. J. Immunol. 127, 1075-1080. Feng, X., Tonnesen, M. G., Peerschke, E. I. B., and Ghebrehiwet, B. (2002). Cooperation of C1q receptors and integrins in C1q-mediated endothelial cell adhesion and spreading. J. Immunol. 168, 2441-2448. Ghebrehiwet, B., Lim, B.-L., Kumar, R., Feng, X., and Peerschke, E. I. B. (2001). gC1q-R/p33: A member of a new class of multifunctional and multicompartmental cellular proteins is involved in inflammation and infection. Immunol. Rev. 180, 65-77. This is an up-to-date and detailed summary of the structure and function of gC1q-R/p33 as well as cClq-R/CR with 76 relevant references.
Guo, W.-X., Ghebrehiwet, B., Weksler, B., Schweizer, K., and Peerschke, E. I. B. (1999). Upregulation of endothelial cell binding proteins/receptors for complement C1q by inflammatory cytokines. J. Lab. Clin. Med. 133, 541-550.
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Silverstein, R. L. (1999). The vascular endothelium. In: Inflammation: Basic Principles and Clinical Correlates, J. I. Gallin and R. Snyderman, eds., p. 207. This is an excellent reference and extensively describes the role of endothelial cells in inflammation.
van den Berg, R. H., Faber-Krol, M. C., Sim, R. B., and Daha, M. R. (1998). The first subcomponent of complement, C1q, triggers the production of IL-8, IL-6 and monocyte chemoattractant peptide-1 by human umbilical vein endothelial cells. J. Immunol. 161, 6924-6930. This report is the first to describe the Clq-mediated release of important cytokines from endothelial cells and has a very well balanced bibliography.
Dr. Ghebrehiwet is a Professor in the Department of Medicine at Stony Brook University, and his laboratory focuses on the biological response as a consequence of the interaction between C1q and cell surface proteins. He is credited with having discovered and characterized both cC1q-R (which is identical to calreticulin) and gC1q-R as ubiquitously distributed, multifunctional C1q binding cell surface proteins.
Dr. Ellinor Peerschke is Professor of Pathology at Weill Medical College of Cornell University in New York. Her research focuses primarily on blood platelet and vascular endothelial cell function in hemostasis, thrombosis, and inflammation.
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