Disease relevance of C3

• This longitudinal study explored whether C3 predicts a large weight gain in middle-aged men [1].
• Cross-sectional studies of humans have reported correlations between C3 and obesity [1].
• Both jijoye lines were superinfectable, inducible, and carried EBV and C3 receptors [2].
• Variations in the C3, C3a receptor, and C5 genes affect susceptibility to bronchial asthma [3].
• Levels of the d split product of C3 (C3d) were increased in 14 of 19 patients with rheumatoid arthritis and in 6 of 20 Crohn's disease patients [4].

Psychiatry related information on C3

• The levels and cellular localization of mRNA for complement C1q and C3 were examined by RNA gel blot and nonradioactive in situ hybridization in the frontal cortex of patients with Alzheimer's disease (AD) and age-matched controls [5].

High impact information on C3

• Its effect was enhanced by the third component (C3) of the complement system, but the fifth component (C5) had no effect [6].
• Human cells express C-regulatory proteins, CD46 and CD55, thereby circumventing attack by C3, a major effector of C [7].
• Receptors for the Fc portion of immunoglobulins or for the third component of complement (C3) are present on a variety of circulating and fixed tissue cells including granulocytes, monocytes, lymphocytes and glomerular epithelial cells [8].
• We recently reported that infection by HSV-1 induces both Fc and C3 receptors on human endothelial cells [8].
• It is a cell-surface macromolecule (labelled with 125I and lactoperoxidase) which, in its isolated state, retains the ability to bind both C3 and C3b [9].

Chemical compound and disease context of C3

• Linkage relationships of the insulin receptor gene with the complement component 3, LDL receptor, apolipoprotein C2 and myotonic dystrophy loci on chromosome 19 [10].
• Liver biopsies of a 58-year-old clinically healthy patient with a hepatomegaly and intracisternal PAS-negative globular hyaline bodies were immunofluorescent-optically examined for the content of the complement components C 1 q, C 4, C 9, C 1-inactivator, C 3-activator [11].
• We also report that solubilized gC-2, the genetically related glycoprotein specified by HSV-2, binds to iC3-Sepharose. mAb specific for gC-1 or gC-2 and mutant viral strains were used to identify the C3-binding glycoproteins [12].
• In contrast, related Moraxella subspecies (n = 13) or other human pathogenic bacteria (n = 13) do not bind C3 or methylamine-treated C3 [13].
• The ability of antigranulocyte antibody to fix the third component of complement (C3) to the granulocyte surface was investigated by an assay that quantitates the binding of monoclonal anti-C3 antibody to paraformaldehyde-fixed cells preincubated with Felty's syndrome serum in the presence of human complement [14].

Biological context of C3

• These data provide evidence that regulated gamete-induced generation of C3 fragments and the binding of these fragments by selectively expressed receptors on sperm and oocytes may be an initial step in gamete interaction, leading to membrane fusion and fertilization [15].
• C3b2-IgG complexes are formed during complement activation in serum by attachment of two C3b molecules (the proteolytically activated form of C3) to one IgG heavy chain (IgG HC) via ester bonds [16].
• They also indicate that some or all of the C3 residues that are directly involved in, or contribute to, the structure of one of the CR1 and H binding sites are located within residues 727-768 [17].
• Likewise, dimeric C3b is known to enhance complement receptor 1-dependent phagocytosis, and dimeric C3d (the smallest thioester-containing fragment of C3) linked to a protein antigen facilitates CR2-dependent B-cell proliferation [16].
• Amino acid sequence data placed the Mr 17,000 fragment within residues 1385 to 1540 of the C3 sequence [18].

Anatomical context of C3

• The virus is thought to exclusively bind to B lymphocytes and epithelial cells via receptors (CR2/CD21) that also interact with fragments of the third component of complement (C3) [19].
• Identification of an additional class of C3-binding membrane proteins of human peripheral blood leukocytes and cell lines [20].
• On neutrophils and mononuclear phagocytes, CR1 is the predominant C3-binding glycoprotein, but gp45-70 is present on both cell populations and on macrophage and neutrophil cell lines [20].
• The C3d domain of C3 contains the site that binds to the C3d receptor (CR2) which is expressed on B lymphocytes [21].
• Furthermore, human and hamster oocytes can activate the alternative pathway of complement and also bind human C3 fragments [15].

Associations of C3 with chemical compounds

• This interaction is specific as evidenced by inhibition with nonconjugated virus, anti-CR2 antibodies, aggregated C3, and an antibody to the gp350 viral glycoprotein that the virus uses to bind to CR2 [19].
• To characterize the interaction of VCP with C3 and C4 and understand the mechanism by which VCP inactivates complement, we have expressed VCP in a yeast expression system and compared the biologic activity of the purified protein to that of human factor H and complement receptor 1 (CR1) [22].
• Expression and characterization of the C345C/NTR domains of complement components C3 and C5 [23].
• In the presence of 1 M epsilon-amino-caproic acid (EACA) spontaneous C3 cleavage is considerably enhanced and accompanied by the appearance of biologically active C3a [24].
• This is concluded from the finding that C3 inactivation is prevented by EDTA, by elimination of properdin factor B, and unimpaired in C4 deficient guinea pig serum [24].

Physical interactions of C3

• The interactions of properdin with both surface-bound and fluid-phase C3 (the third component of complement) and its activation products have been investigated by using a purified preparation of the 'native' form [25].
• Alterations in C3 activation and binding caused by phosphorylation by a casein kinase released from activated human platelets [26].
• Sequencing of amino-terminal and internal peptides from the C3-binding protein disclosed a proline-rich region spanning approximately 20 amino acids and a signal peptide that had not been previously reported [27].
• These results clearly demonstrate that C3/C4 gene duplication and linkage between the C4 gene and the major histocompatibility complex predate mammalian/amphibian divergence [28].
• A protein drp90 encoded on the leftwards strand of soybean nodule urate oxidase cDNA binds to a regulatory sequence in leghemoglobin C3 gene [29].

Enzymatic interactions of C3

• C3 that had been phosphorylated with platelet casein kinase was tested for its susceptibility to cleavage by trypsin or the classical and alternative pathway convertases and its binding to EAC and IgG [26].
• In this communication, we report that MASP is unique in having the proteolytic capacity to cleave C3 with subsequent activation of the alternative pathway, a capacity which C1s lacks [30].
• Plasma membrane elastase and cathepsin G from U937 cells cleave C3 into C3a- and C3b-like fragments; further incubation leads to C3c- and C3dg-like fragments, as judged from SDS-PAGE analysis of the digests [31].

Regulatory relationships of C3

• CD40 ligation is able to enhance C3 secretion by PTEC [32].
• Inhibition of NF-kappaB offset CD40L-induced C3 secretion by 70% [32].
• RESULTS: Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18 [33].
• In serum the inhibitory effect of 1 M EACA on C3bINA appears to allow escape of the properdin system from its control and thus to increase its net activity toward C3 despite inhibition of the enzymic reactions proper [24].
• The greatest magnitude of C3 secretion was induced by the combination of IL-1beta and IL-6 [34].

Other interactions of C3

• The structure supports a model whereby the transition of native C3 to its functionally active state involves the disruption of a complementary domain interface and provides insight into the basis for the interaction between C3d and CR2 [35].
• Rare variants were observed in the C3, Tf, and Pi systems [36].
• In addition, antibodies to both MCP and C3 significantly inhibited penetration of hamster oocytes by human sperm [15].
• Complement components C3, C4, and C5 are members of the thioester-containing alpha-macroglobulin protein superfamily [23].
• MT1-MMP proteolysis liberates the deposited C3 activation fragments from the cell surface [37].

Analytical, diagnostic and therapeutic context of C3

• Proteins binding the third component of complement (C3) were isolated by affinity chromatography from surface-labeled solubilized membranes of human peripheral blood cells and cell lines [20].
• Secreted C3 was assayed by ELISA and a functional hemolytic test on supernatants [32].
• Analysis of C3 gene expression was evaluated by reverse-transcription PCR and Northern blot [32].
• The aim of the study was to investigate the putative action of CD40 ligation on enhancement of C3 secretion by PTEC [32].
• The results of this SNP case-control study suggested an association between 4896C/T in the C3 gene and atopic childhood BA (P = 0.0078) as well as adult BA (P = 0.010) [3].

References