Up-regulation of endothelial cell binding proteins/receptors for complement component C1q by inflammatory cytokines

• Published in: The Journal of laboratory and clinical medicine 1999-06, Vol.133 (6), p.541-550
• Main Authors: Guo, Wei-Xing, Ghebrehiwet, Berhane, Weksler, Babette, Schweitzer, Karin, Peerschke, Ellinor I.B
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blotting, Northern; Blotting, Western; Bone Marrow Cells - metabolism; Bone Marrow Cells - physiology; Carrier Proteins; Cell Division; Cell Line; Complement C1q - metabolism; Cytokines - pharmacology; Cytokines - physiology; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Escherichia coli - chemistry; Fundamental and applied biological sciences. Psychology; Humans; Hyaluronan Receptors; Inflammation; Inflammation - metabolism; Interferon-gamma - pharmacology; Lipopolysaccharides - pharmacology; Membrane Glycoproteins; Microcirculation; Mitochondrial Proteins; Molecular and cellular biology; Receptors, Complement - metabolism; Recombinant Proteins; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Up-Regulation
• ISSN: 0022-2143; 1931-5244; 1532-6543; 1878-1810
• DOI: 10.1016/S0022-2143(99)90183-X

Endothelial cells express a variety of receptor systems involved in humoral defense, including receptors for the collagen-like and globular domains of the complement component C1q, designated cC1qR and gC1qR, respectively. In the present study a microvascular endothelial cell line was used to test the hypothesis that expression of these C1q-binding proteins may be affected by vascular inflammatory reactions. The results demonstrate that the expression of both cC1qR and gC1qR by bone marrow vascular endothelial cells is up-regulated by inflammatory mediators, interferon-γ, tumor necrosis factor-α, and lipopolysaccharide (Escherichia coli, 055:B5) in a dose- and time-dependent manner, as detected by enzyme-linked immunosorbent assay. cC1qR and gC1qR expression increased significantly (P < .05) within 4 to 7 hours and doubled after 22 hours of stimulation. 3H-thymidine incorporation studies and direct cell counts confirmed that increased C1qR expression was not due to increased cell proliferation. Northern blot analysis revealed that the up-regulation of cC1qR and gC1qR protein expression was preceded by increases in corresponding mRNA levels, suggesting increased gene transcription. Indeed C1qR mRNA up-regulation was prevented by actinomycin D, and C1qR protein synthesis was inhibited by cycloheximide. Bone marrow vascular endothelial cell exposure to C1q, however, did not alter cC1qR or gC1qR expression, but up-regulation of the leukocyte adhesion molecule ICAM-1 was noted in the presence of aggregated C1q. The up-regulation of C1qR by inflammatory mediators and the ability of C1q itself to increase ICAM-1 expression suggest a potential role for these binding sites in vascular inflammation and immune injury.