Expression of a complete and functional complement system by human neuronal cells in vitro

Citation
A. Thomas et al., Expression of a complete and functional complement system by human neuronal cells in vitro, INT IMMUNOL, 12(7), 2000, pp. 1015-1023
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INTERNATIONAL IMMUNOLOGY
ISSN journal
0953-8178 → ACNP
Volume
12
Issue
7
Year of publication
2000
Pages
1015 - 1023
Database
ISI
SICI code
0953-8178(200007)12:7<1015:EOACAF>2.0.ZU;2-E
Abstract
We demonstrate in vitro expression of complement components, i.e. C3, facto r H (FH), factor B (FB), C4, C1-inhibitor (C1-inh), C1q, C5, C6, C7 and C9, by four human neuroblastoma cell lines IMR32, SKNSH, SH-SY5Y and KELLY, Ac tivating proteins C4, C9 and Clq, and regulatory proteins FH and C1-inh wer e produced constitutively by the four cell lines. C3, C6 and FB were mainly produced by SKNSH and SH-SY5Y, Western blot experiments showed that secret ed proteins were structurally similar to their serum counterparts. An addit ional polypeptide of 43 kDa with FH immunoreactivity was detected, which co uld correspond to the N-terminal truncated form found in plasma. Regulation of complement expression by inflammatory cytokines, lipopolysaccharide and dexamethasone was tested in vitro. These factors had no significant effect s on activating synthesis of components C3, FB and C4, but expression of re gulating components C1-inh and FH was strongly increased particularly by IF N-gamma and tumor necrosis factor-alpha. The rate of synthesis of complemen t components was dependent on the differentiation of neuroblastoma cells. T his effect of differentiation was also observed on normal rat neurons. Rat cerebellar granule cells constitutively expressed mRNA for C4 and C1q, but expression of C3 mRNA was induced by differentiation. This study shows that neurons could be another local source of complement in the brain, besides astrocytes and microglia, Human neuroblastoma cell lines can constitute an interesting model to analyze complement biosynthesis by human neurons. Loca l complement expression by neurons in vivo may be implicated in some physio -pathological processes.