Disease relevance of C7

• No evidence for association of multiple sclerosis with the complement factors C6 and C7 [1].
• Fatal pyoderma gangrenosum in association with C7 deficiency [2].
• Hereditary deficiency of the seventh component of complement and recurrent meningococcal infection: investigations of an Irish family using a novel haemolytic screening assay for complement activity and C7 M/N allotyping [3].
• We describe an 11-year-old girl suffering from recurrent meningitis with a complete absence of the seventh component of complement (C7) [4].
• After determination of long terminal repeat (LTR) sequences and adjacent chromosomal integration sites by inverse PCR techniques, two HERV-K type 2 proviruses displaying long retroviral open reading frames (ORFs) were assigned to chromosomes 7 (C7) and 19 (C19) by using a human-rodent monochromosomal cell hybrid mapping panel [5].

High impact information on C7

• In addition, the simultaneous occurrence of two hereditary complement deficiencies (C2 and C7) was discovered in one family of this remarkable kindred [6].
• The serum of a 44-yr-old woman of French-Canadian descent having a B-27 positive ankylosing spondylitis was deficient in the seventh component of complement (C7) as determined by hemolytic and immunochemical methods [6].
• A physical map of the C6 and C7 complement component gene region on chromosome 5p13 [7].
• Complement component C5 binds to components C6 and C7 in reversible reactions that are distinct from the essentially nonreversible associations that form during assembly of the complement membrane attack complex (MAC) [8].
• We suggested from these and other observations that binding of the C345C module of C5 to the FIMs of C7, but not C6, is also essential for MAC assembly itself [8].

Biological context of C7

• We have determined the structure of the C7 gene, which is encoded by 18 exons whose sizes vary from 56 to 244 bp [9].
• Gene deletion of C7 was not found in the cell lines by Southern blot analysis [10].
• Our findings suggest a possible relationship between oesophageal tumorigenesis and reduced expression of C6 and C7 mRNAs, which is probably caused by a change in gene expression regulation and not by genetic loss of the locus [10].
• Data from this study show that the genes encoding the human terminal complement components C6, C7, and C9 define a cluster in the short arm of chromosome 5 [11].
• The Israeli C7-deficient cases all share a C7 haplotype and are homozygous for a mis-sense mutation in exon 9 [12].

Anatomical context of C7

• In situ hybridisation confirmed the localisation of C7 mRNA in normal oesophageal epithelial cells and its disappearance in tumour cells [10].
• Organ-specific contribution to circulating C7 levels by the bone marrow and liver in humans [13].
• Deficiencies of C7 can be associated with decreased neutrophil chemotaxis, phagocytosis, and opsonization, similar to the immunologic abnormalities described in patients with PG [2].
• Cerebral endothelial cells and HUVEC expressed detectable levels of complement gene mRNAs for the C1q B-chain, C1r, C1s, C2, C3, C4, C5, C7, C8 gamma-subunit and C9 [14].
• A proportion of C7 secreted by HUVEC was incorporated into the terminal complement complex (TCC) assembled spontaneously in the supernatant of cells cultured in C7-deficient human serum, and was not detected by the standard ELISA for C7 measurement [15].

Associations of C7 with chemical compounds

• Chemical cross-linking using a cleavable radioiodinated photoreactive reagent revealed that both C6 and C7 associate preferentially with the alpha'-chain of C5b [16].
• Polyclonal antibodies directed against C5c blocked the interaction of C5b-6 with C7, whereas antibodies directed against C5d inhibited the binding of C5 with C3b [16].
• When mRNA expressions of other components were examined by means of semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in 10 tumour/normal pair specimens, significant reductions in C6 and C7 mRNAs were observed, while C3 and C5 mRNAs were enhanced in both normal and tumour tissues [10].
• Using a radioiodinated photoreactive cross-linking reagent bound to the polar head group of phosphatidylethanolamine, the stalk part of the C5b-7 complex could be labeled preferentially, and it was found to consist mainly of C6 and C7 [17].
• Synthesis of C7 by HUVEC was confirmed by inhibition experiments in the presence of cycloheximide and by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of C7 mRNA expression [15].

Physical interactions of C7

• These results indicate that, like C6, the FIMs alone in C7 mediate reversible binding to C5 [18].

Other interactions of C7

• The other important finding is that in C6, C7, C8, and C9 Trp residues without a second Trp (or another aromatic residue) at the +3 position can be C-mannosylated [19].
• These results show that clusterin exerts its inhibitory effect by interacting with a structural motif common to C7, C8 alpha, and C9b [20].
• Radioligand binding studies revealed that the isolated component, as well as C7 after its incorporation into the terminal complement complex C5b-9, can bind plasminogen [21].
• Complement component C7 is a plasminogen-binding protein [21].
• C7 was also detected by amplifying part of the human gene in hybrid DNA using the polymerase chain reaction [22].

Analytical, diagnostic and therapeutic context of C7

• Using surface plasmon resonance, we found that rC7-FIMs binds specifically to both C5 and the rC5-C345C domain with K(D) approximately 50 nM, and competes with C7 for binding to C5, as expected for an active domain [18].
• In the bone marrow transplant group, one informative transplant was identified and donor-derived C7 was detected by enzyme-linked immunosorbent assay [13].
• Conversion from recipient to donor allotype following organ transplantation has demonstrated the synthetic sites of several complement proteins, but in the case of C7 this was not possible until recently [13].
• Bone marrow and hepatic C7 production was quantified in bone marrow transplant and liver transplant recipients, respectively, where a mismatch for the C7 allotypes distinguished by the monoclonal antibody had occurred [13].
• Electrophoretic mobility shift assays suggested that the binding of the C/EBPalpha transcription factor to a C/EBP sequence located at +42 is essential for C7 expression [23].

References