PubMed · 363219
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P J Lachmann, M J Hobart. 1978. Complement genetics in relation to HLA.. https://doi.org/10.1093/oxfordjournals.bmb.a071505
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In a previous study the authors demonstrated that the production of complement component C4 by human kidney proximal tubular epithelial cells (PTEC) is upregulated by interferon gamma (IFN-gamma). In the present study the authors describe that PTEC in culture express both mRNA and protein of the IFN-gamma receptor complex, and that culture of PTEC with 1000 U/ml IFN-gamma for 72 h results in enhanced production not only of C4 (36.1 ng/10(6) cells), but also of C2 (10.8 ng/10(6) cells) and Factor H (17.5 ng/10(6) cells). Unstimulated PTEC produced 0.5 ng/10(6) cells, 0.5 ng/10(6) cells and 0.4 ng/10(6) cells of C2, C4 and Factor H, respectively. The upregulation of the three complement components was dose- and time-dependent and specific for IFN-gamma because the effect of IFN-gamma was abolished by a monoclonal antibody directed against IFN-gamma. Furthermore no effect of other cytokines was observed. The regulation of synthesis of C2, C4 and Factor H occurred at the transcriptional level as shown by semi-quantitative RT-PCR and dot-blot analysis. Taken together with the observation that in normal kidney tissue the tubuli express IFN-gamma receptor alpha-chain and a signal transducing protein, the present study implies that enhanced production of complement by PTEC may occur during a local immune response by in situ generation of IFN-gamma by infiltrating T-cells in the interstitium of the kidney.
The distribution of four serum complement component polymorphisms (BF, C2, C3 and C4) were examined in two geographically separated populations, one from Tasmania (Australia) and the other from northeast England. The differences in genotypic frequencies between them at all 4 loci are not statistically significant (p > 0.05). When C4 haplotypes were investigated, only one (C4A4-C4B2) exhibited significant linkage disequilibrium (p = 0.0006 after correction, p = 0.01), and this was only observed in Tasmanians. The English population exhibited a larger number of alleles across the four loci used in this study than the Tasmanian, and this may well reflect a bottle-neck effect and the greater relative isolation of the population of the island State of Australia. Overall, the findings confirm the close relationship between immigrants from the British Isles to Tasmania.
Activation of the alternative complement pathway of serum produces complexes of properdin (P) and C3 as measured in a double antibody enzyme-linked immunosorbent assay. When purified from serum, these complexes decrease factor B hemolytic activity in serum and do not restore the alternative pathway hemolytic activity of serum deficient in P. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of activated serum containing biotinylated P, followed by blotting to nitrocellulose and development with streptavidin-alkaline phosphatase revealed a band at 53 kDa for monomeric P and an additional band at 160 kDa. P samples eluted from zymosan and purified from activated serum revealed a band at 116 kDa for C3 alpha and 74 kDa for C3 beta, and an additional band at 160 kDa when analyzed by SDS-PAGE, Western blotting and development with antibody to C3. The appearance of a 160 kDa band containing P and C3 indicates that these proteins are contained in a complex formed during activation of the alternative pathway. Activation of a purified reagent mixture containing factors B, D, and H, and 125I-labeled P or 125I-labeled C3, followed by SDS-PAGE and autoradiography confirmed the presence of a 160-kDa band which disappeared following hydroxylamine treatment of the sample. These data are consistent with a covalent linkage of C3 to P via the C3 alpha chain, producing the 160-kDa complex.