Complement expression in human brain. Biosynthesis of terminal pathway components and regulators in human glial cells and cell lines.
C biosynthesis at extrahepatic sites remote from plasma C may be important in the protection of tissues against inflammation and infection but may also contribute to tissue injury. This latter possibility is particularly relevant in the central nervous system (CNS), where several cell types are susceptible to damage by C. We have previously shown that human astrocyte-derived tumor cell lines synthesize and secrete all of the components of the activation pathways of C. In this study, we demonstrate that these cells also produce the components (C6, C7, C8, and C9) and regulators (S-protein and clusterin) of the lytic terminal C pathway. The terminal components produced are hemolytically active, and secretion is markedly up-regulated by the inflammatory cytokine IFN-gamma. Primary human fetal astrocytes also expressed C6, C7, S-protein, and clusterin. The human monocyte/macrophage cell line, used here as a model for microglia, also produced all terminal components and regulators when appropriately stimulated. These studies raise the prospect of the intrathecal synthesis of a complete, functional C system and its regulators in the inflamed CNS. Intrathecal C synthesis may be important in the resolution of infection and inflammation but, given the C susceptibility of some CNS cell types, may also exacerbate damage in demyelination and neurodegeneration.
Gasque
P
P
Department of Medicine Biochemistry, University of Wales College of Medicine, Cardiff, United Kingdom.
Fontaine
M
M
Morgan
B P
BP
D000911:Antibodies, Monoclonal; D001253:Astrocytes / Q000276:immunology; D001921:Brain / Q000276:immunology*; D002460:Cell Line; D051152:Clusterin; D003169:Complement Inactivator Proteins / Q000096:biosynthesis; D015938:Complement Membrane Attack Complex / Q000096:biosynthesis; D003165:Complement System Proteins / Q000096:biosynthesis*; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007158:Immunologic Techniques; D007371:Interferon-gamma / Q000502:physiology; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D017628:Microglia / Q000276:immunology; D018832:Molecular Chaperones; D009457:Neuroglia / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000096:biosynthesis; D019096:Vitronectin
D000911:Antibodies, Monoclonal; D051152:Clusterin; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins; D006023:Glycoproteins; D007371:Interferon-gamma; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D012313:RNA; D019096:Vitronectin; C495242:CLU protein, human