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C3  -  complement component 3

Mus musculus

Synonyms: AI255234, ASP, Complement C3, HSE-MSF, Plp, ...
 
 
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Disease relevance of C3

  • Complement C4 is protective for lupus disease independent of C3 [1].
  • We induced the passive reverse Arthus reaction to IgG immune complexes (IC) at different tissue sites in mice lacking C3 treated or not with a C5aR-specific antagonist, or in mice lacking mast cells (Kit(W)/Kit(W-v) mice), and compared the inflammatory responses with those in the corresponding wild-type mice [2].
  • The role of complement C3 in mediating systemic lupus erythematosus (SLE) was examined using a double-knockout C3(null)C4(null) Fas (CD95)-deficient mouse model [1].
  • The alternative activation pathway and complement component C3 are critical for a protective immune response against Pseudomonas aeruginosa in a murine model of pneumonia [3].
  • OBJECTIVE: To investigate the effect of complement deficiency on atherogenesis and lipidemia, we used mice deficient in the third complement component (C3-/-) or factor B (FB-/-) [4].
 

Psychiatry related information on C3

  • The third component of complement C3 and its fragments have a central role in a variety of host defense mechanisms [5].
  • Further, the synthesis of C3 was increased 5-10-fold in response to various synthetic peptides corresponding to the amyloid beta/A4 protein, which is the main constituent of extracellular amyloid deposits in Alzheimer's disease (AD) [6].
 

High impact information on C3

  • There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-R1(+) spleen macrophages, and formation of C3 ligands [7].
  • A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial binding C3 fragments recognized by leukocytes [7].
  • Surprisingly, conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously [7].
  • Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H [8].
  • This pathway is triggered by the hydrolysis of C3, resulting in the formation of C3 convertase [8].
 

Chemical compound and disease context of C3

 

Biological context of C3

  • Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution [13].
  • Interleukin 6 influences germinal center development and antibody production via a contribution of C3 complement component [14].
  • C3- or C5-deficient mice exhibited high mortality, parenchymal damage, and impaired liver regeneration after partial hepatectomy [13].
  • The development of severe SLE in the absence of both classical and alternative complement pathways suggests that it is the absence of C4, and not the presence of C3, that is critical in SLE pathogenesis [1].
  • Collectively, these results indicate that complement activation by the alternative pathway is critical for the survival of mice infected with P. aeruginosa and that the protection provided by complement is at least in part due to C3-mediated opsonization and phagocytosis of P. aeruginosa [3].
 

Anatomical context of C3

  • In addition, germinal center cells isolated from C3-deficient mice produced a similar defect in isotype production [14].
  • The IC-mediated slow leukocyte rolling velocity and subsequent adhesion and emigration are dependent on Fcgamma receptors (FcgammaRs), particularly FcgammaRIII, with complement C3 and C5 having no detectable role [15].
  • Finally, we demonstrated that C3 contributed to the elicitation of neutrophils to alveoli, which corresponded to an increased synthesis of TNF-alpha, macrophage-inflammatory protein-2, and cytokine-induced neutrophil chemoattractant [2].
  • Together, the phenotypes of C3(-/-) mice and Kit(W)/Kit(W-v) mice suggest that complement and mast cells have distinct tissue site-specific requirements acting by apparently distinct mechanisms in the initiation of IC inflammation [2].
  • In mice, C3 (the precursor to ASP) knockout results in ASP deficiency and leads to reduced body fat and leptin levels [16].
 

Associations of C3 with chemical compounds

  • Our initial study indicated that complement C3-deficient (-/-) mice (and, therefore, ASP deficient) demonstrated altered dietary postprandial triglyceride clearance [17].
  • Ovarian steroid-regulated synthesis and secretion of complement C3 and factor B in mouse endometrium during the natural estrous cycle and pregnancy period [18].
  • Expression of C3 was remarkably enhanced, whereas that of Bf changed only slightly, after injection of combined estrogen and progesterone to ovariectomized animals [18].
  • These factors have been shown to influence the formation of acylation-stimulating protein (ASP), a cleavage product of complement C3 [19].
  • Both human and murine adipocytes express mRNA and/or protein for the complement components C3 and factors B and D (adipsin) required to generate ASP [20].
 

Physical interactions of C3

  • Distinct tissue site-specific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex-induced injury of skin and lung [2].
 

Regulatory relationships of C3

  • Acylation-stimulating protein (ASP) deficiency induces obesity resistance and increased energy expenditure in ob/ob mice [16].
  • Cis- and trans-acting elements required for constitutive and cytokine-regulated expression of the mouse complement C3 gene [21].
  • Synthetic Alzheimer amyloid beta/A4 peptides enhance production of complement C3 component by cultured microglial cells [6].
 

Other interactions of C3

  • A second alteration involved impaired de novo synthesis of C3 both in serum and germinal center cells from IL-6-deficient mice [14].
  • Factor B(-/-) mice, but not C4(-/-) mice, infected with P. aeruginosa had a mortality rate similar to that of C3(-/-) mice, indicating that in this model the alternative pathway of complement activation is required for the host defense against Pseudomonas infection [3].
  • The C3-/- mice also had 58% higher serum triglyceride levels (P<0.05) and a more proatherogenic lipoprotein profile, with significantly more low-density lipoprotein cholesterol and very-low-density lipoprotein triglycerides than control mice [4].
  • We have recently shown that mouse erythrocytes deficient in the membrane C3 regulatory protein, complement receptor 1-related gene/protein y (Crry), but not decay-accelerating factor (DAF), were spontaneously eliminated in vivo by complement [22].
  • Anti-GBM antibody administration in sensitised wild-type mice resulted in deposition of immune complexes and complement factor 3, followed by increased ICAM-1 and VCAM-1 expression and influx of polymorphonuclear leucocytes [23].
 

Analytical, diagnostic and therapeutic context of C3

References

  1. Complement C4 is protective for lupus disease independent of C3. Einav, S., Pozdnyakova, O.O., Ma, M., Carroll, M.C. J. Immunol. (2002) [Pubmed]
  2. Distinct tissue site-specific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex-induced injury of skin and lung. Baumann, U., Chouchakova, N., Gewecke, B., Köhl, J., Carroll, M.C., Schmidt, R.E., Gessner, J.E. J. Immunol. (2001) [Pubmed]
  3. The alternative activation pathway and complement component C3 are critical for a protective immune response against Pseudomonas aeruginosa in a murine model of pneumonia. Mueller-Ortiz, S.L., Drouin, S.M., Wetsel, R.A. Infect. Immun. (2004) [Pubmed]
  4. Lack of complement factor C3, but not factor B, increases hyperlipidemia and atherosclerosis in apolipoprotein E-/- low-density lipoprotein receptor-/- mice. Persson, L., Borén, J., Robertson, A.K., Wallenius, V., Hansson, G.K., Pekna, M. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  5. Expression of polypeptide segments of the human complement component C3 in E. coli: genetic and immunological characterization of cDNA clones specific for the alpha-chain of C3. Ma, D., Sessler, M.J., Meyer, T.F., Schrod, L., Hänsch, G.M., Burger, R. J. Immunol. (1985) [Pubmed]
  6. Synthetic Alzheimer amyloid beta/A4 peptides enhance production of complement C3 component by cultured microglial cells. Haga, S., Ikeda, K., Sato, M., Ishii, T. Brain Res. (1993) [Pubmed]
  7. A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q. Kang, Y.S., Do, Y., Lee, H.K., Park, S.H., Cheong, C., Lynch, R.M., Loeffler, J.M., Steinman, R.M., Park, C.G. Cell (2006) [Pubmed]
  8. Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H. Pickering, M.C., Cook, H.T., Warren, J., Bygrave, A.E., Moss, J., Walport, M.J., Botto, M. Nat. Genet. (2002) [Pubmed]
  9. Local extrahepatic expression of complement genes C3, factor B, C2, and C4 is increased in murine lupus nephritis. Passwell, J., Schreiner, G.F., Nonaka, M., Beuscher, H.U., Colten, H.R. J. Clin. Invest. (1988) [Pubmed]
  10. Cutting edge: the absence of C3 demonstrates a role for complement in Th2 effector functions in a murine model of pulmonary allergy. Drouin, S.M., Corry, D.B., Kildsgaard, J., Wetsel, R.A. J. Immunol. (2001) [Pubmed]
  11. Cellular specificity of murine renal C3 expression in two models of inflammation. Ault, B.H., Colten, H.R. Immunology (1994) [Pubmed]
  12. Synergistic effect of romurtide with ampicillin against pneumococcal pneumonia in mice. Nakajima, R., Namba, K., Ishida, Y., Katsuma, E., Otani, T., Osada, Y. Chemotherapy. (1992) [Pubmed]
  13. The proinflammatory mediators C3a and C5a are essential for liver regeneration. Strey, C.W., Markiewski, M., Mastellos, D., Tudoran, R., Spruce, L.A., Greenbaum, L.E., Lambris, J.D. J. Exp. Med. (2003) [Pubmed]
  14. Interleukin 6 influences germinal center development and antibody production via a contribution of C3 complement component. Kopf, M., Herren, S., Wiles, M.V., Pepys, M.B., Kosco-Vilbois, M.H. J. Exp. Med. (1998) [Pubmed]
  15. C1q governs deposition of circulating immune complexes and leukocyte Fcgamma receptors mediate subsequent neutrophil recruitment. Stokol, T., O'Donnell, P., Xiao, L., Knight, S., Stavrakis, G., Botto, M., von Andrian, U.H., Mayadas, T.N. J. Exp. Med. (2004) [Pubmed]
  16. Acylation-stimulating protein (ASP) deficiency induces obesity resistance and increased energy expenditure in ob/ob mice. Xia, Z., Sniderman, A.D., Cianflone, K. J. Biol. Chem. (2002) [Pubmed]
  17. Reduced body weight, adipose tissue, and leptin levels despite increased energy intake in female mice lacking acylation-stimulating protein. Murray, I., Havel, P.J., Sniderman, A.D., Cianflone, K. Endocrinology (2000) [Pubmed]
  18. Ovarian steroid-regulated synthesis and secretion of complement C3 and factor B in mouse endometrium during the natural estrous cycle and pregnancy period. Li, S.H., Huang, H.L., Chen, Y.H. Biol. Reprod. (2002) [Pubmed]
  19. Increased levels of acylation-stimulating protein in interleukin-6-deficient (IL-6(-/-)) mice. Wernstedt, I., Olsson, B., Jernås, M., Paglialunga, S., Carlsson, L.M., Smith, U., Cianflone, K., Wallenius, K., Wallenius, V. Endocrinology (2006) [Pubmed]
  20. Detection and quantification of the control proteins of the alternative pathway of complement in 3T3-L1 adipocytes. Peake, P.W., O'Grady, S., Pussell, B.A., Charlesworth, J.A. Eur. J. Clin. Invest. (1997) [Pubmed]
  21. Cis- and trans-acting elements required for constitutive and cytokine-regulated expression of the mouse complement C3 gene. Kawamura, N., Singer, L., Wetsel, R.A., Colten, H.R. Biochem. J. (1992) [Pubmed]
  22. Complement-mediated clearance of erythrocytes: mechanism and delineation of the regulatory roles of Crry and DAF. Decay-accelerating factor. Molina, H., Miwa, T., Zhou, L., Hilliard, B., Mastellos, D., Maldonado, M.A., Lambris, J.D., Song, W.C. Blood (2002) [Pubmed]
  23. Failure to induce anti-glomerular basement membrane glomerulonephritis in TNF alpha/beta deficient mice. Ryffel, B., Eugster, H., Haas, C., Le Hir, M. International journal of experimental pathology. (1998) [Pubmed]
  24. Extent of the mouse t complex and its inversions shown by in situ hybridization. Lyon, M.F., Zenthon, J., Evans, E.P., Burtenshaw, M.D., Willison, K.R. Immunogenetics (1988) [Pubmed]
  25. The embryotrophic activity of oviductal cell-derived complement C3b and iC3b, a novel function of complement protein in reproduction. Lee, Y.L., Lee, K.F., Xu, J.S., He, Q.Y., Chiu, J.F., Lee, W.M., Luk, J.M., Yeung, W.S. J. Biol. Chem. (2004) [Pubmed]
  26. Weight gain in relation to plasma levels of complement factor 3: results from a population-based cohort study. Engström, G., Hedblad, B., Janzon, L., Lindgärde, F. Diabetologia (2005) [Pubmed]
 
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