Abstract
Production of the third and fourth components of complement (C3, C4) by smooth muscle cells was investigated by using normal human aortic smooth muscle cells (AoSMC), human smooth muscle cell line (G402) and vascular smooth muscle cells obtained from human umbilical cord vein (UVSMC). AoSMC spontaneously produced both C3 and C4 at 15 ng/10(6) cells/72 hr and 22 ng/10(6) cells/72 hr, respectively, and both were enhanced by interferon-gamma (IFN-gamma). Although phorbol 12-myristate 13-acetate (PMA) and tumour necrosis factor-alpha (TNF-alpha) enhanced C3 production, C4 production was reduced by these agents. On the other hand, G402 produced C4 but not C3 in a dose-dependent manner when cultured with IFN-gamma. UVSMC produced only a small amount of C3 and C4 compared with AoSMC or G402. C3 and C4 produced by AoSMC were confirmed to be identical with their human serum counterparts as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and measurement of haemolytic activity. Northern blotting analysis showed that the expression of mRNA of C3 and C4 was enhanced by TNF-alpha and IFN-gamma, respectively, in AoSMC. Our findings suggest the importance of smooth muscle cells as a source of components of complement in vascular diseases including vasculitis.
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- Alper C. A., Johnson A. M., Birtch A. G., Moore F. D. Human C'3: evidence for the liver as the primary site of synthesis. Science. 1969 Jan 17;163(3864):286–288. doi: 10.1126/science.163.3864.286. [DOI] [PubMed] [Google Scholar]
- Barnum S. R., Ishii Y., Agrawal A., Volanakis J. E. Production and interferon-gamma-mediated regulation of complement component C2 and factors B and D by the astroglioma cell line U105-MG. Biochem J. 1992 Oct 15;287(Pt 2):595–601. doi: 10.1042/bj2870595. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Belt K. T., Carroll M. C., Porter R. R. The structural basis of the multiple forms of human complement component C4. Cell. 1984 Apr;36(4):907–914. doi: 10.1016/0092-8674(84)90040-0. [DOI] [PubMed] [Google Scholar]
- Benzaquen L. R., Nicholson-Weller A., Halperin J. A. Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells. J Exp Med. 1994 Mar 1;179(3):985–992. doi: 10.1084/jem.179.3.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Botto M., Lissandrini D., Sorio C., Walport M. J. Biosynthesis and secretion of complement component (C3) by activated human polymorphonuclear leukocytes. J Immunol. 1992 Aug 15;149(4):1348–1355. [PubMed] [Google Scholar]
- Carroll M. C., Campbell R. D., Bentley D. R., Porter R. R. A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature. 1984 Jan 19;307(5948):237–241. doi: 10.1038/307237a0. [DOI] [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Craddock P. R., Fehr J., Brigham K. L., Kronenberg R. S., Jacob H. S. Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis. N Engl J Med. 1977 Apr 7;296(14):769–774. doi: 10.1056/NEJM197704072961401. [DOI] [PubMed] [Google Scholar]
- Einstein L. P., Hansen P. J., Ballow M., Davis A. E., 3rd, Davis J. S., 4th, Alper C. A., Rosen F. S., Colten H. R. Biosynthesis of the third component of complement (C3) in vitro by monocytes from both normal and homozygous C3-deficient humans. J Clin Invest. 1977 Nov;60(5):963–969. doi: 10.1172/JCI108876. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gaither T. A., Alling D. W., Frank M. M. A new one-step method for the functional assay of the fourth component (C4) of human and guinea pig complement. J Immunol. 1974 Aug;113(2):574–583. [PubMed] [Google Scholar]
- Hill J. H., Ward P. A. The phlogistic role of C3 leukotactic fragments in myocardial infarcts of rats. J Exp Med. 1971 Apr 1;133(4):885–900. doi: 10.1084/jem.133.4.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horiuchi T., Hatta N., Matsumoto M., Ohtsuka H., Collins F. S., Kobayashi Y., Fujita S. Nonsense mutations at Arg-1947 in two cases of familial neurofibromatosis type 1 in Japanese. Hum Genet. 1994 Jan;93(1):81–83. doi: 10.1007/BF00218920. [DOI] [PubMed] [Google Scholar]
- Horiuchi T., Macon K. J., Kidd V. J., Volanakis J. E. cDNA cloning and expression of human complement component C2. J Immunol. 1989 Mar 15;142(6):2105–2111. [PubMed] [Google Scholar]
- Hugli T. E., Müller-Eberhard H. J. Anaphylatoxins: C3a and C5a. Adv Immunol. 1978;26:1–53. doi: 10.1016/s0065-2776(08)60228-x. [DOI] [PubMed] [Google Scholar]
- Kulics J., Circolo A., Strunk R. C., Colten H. R. Regulation of synthesis of complement protein C4 in human fibroblasts: cell- and gene-specific effects of cytokines and lipopolysaccharide. Immunology. 1994 Aug;82(4):509–515. [PMC free article] [PubMed] [Google Scholar]
- Kulics J., Colten H. R., Perlmutter D. H. Counterregulatory effects of interferon-gamma and endotoxin on expression of the human C4 genes. J Clin Invest. 1990 Mar;85(3):943–949. doi: 10.1172/JCI114523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lappin D. F., Guc D., Hill A., McShane T., Whaley K. Effect of interferon-gamma on complement gene expression in different cell types. Biochem J. 1992 Jan 15;281(Pt 2):437–442. doi: 10.1042/bj2810437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
- Senger D. R., Hynes R. O. C3 component of complement secreted by established cell lines. Cell. 1978 Oct;15(2):375–384. doi: 10.1016/0092-8674(78)90006-5. [DOI] [PubMed] [Google Scholar]
- Stecher V. J., Thorbecke G. J. Sites of synthesis of serum proteins. 3. Production of beta-1-C, beta-1-E and transferrin by primate and rodent cell lines. J Immunol. 1967 Oct;99(4):660–668. [PubMed] [Google Scholar]
- Strunk R. C., Cole F. S., Perlmutter D. H., Colten H. R. gamma-Interferon increases expression of class III complement genes C2 and factor B in human monocytes and in murine fibroblasts transfected with human C2 and factor B genes. J Biol Chem. 1985 Dec 5;260(28):15280–15285. [PubMed] [Google Scholar]
- Suzuki T., Cooper M. D. Comparison of the expression of IL 2 receptors by human T and B cells: induction by the polyclonal mitogens, phorbol myristate acetate, and anti-mu antibody. J Immunol. 1985 May;134(5):3111–3119. [PubMed] [Google Scholar]
- Tsukamoto H., Nagasawa K., Ueda Y., Mayumi T., Yoshizawa S., Furugo I., Tsuru T., Niho Y. Effect of T cells on the complement production by monocytes. Cell Immunol. 1993 Feb;146(2):382–390. doi: 10.1006/cimm.1993.1034. [DOI] [PubMed] [Google Scholar]
- Tsukamoto H., Nagasawa K., Yoshizawa S., Tada Y., Ueda A., Ueda Y., Niho Y. Synthesis and regulation of the fourth component of complement (C4) in the human monocytic cell line U937: comparison with that of the third component of complement (C3). Immunology. 1992 Apr;75(4):565–569. [PMC free article] [PubMed] [Google Scholar]
- Tsukamoto H., Ueda A., Nagasawa K., Tada Y., Niho Y. Increased production of the third component of complement (C3) by monocytes from patients with systemic lupus erythematosus. Clin Exp Immunol. 1990 Nov;82(2):257–261. doi: 10.1111/j.1365-2249.1990.tb05436.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watanabe I., Horiuchi T., Fujita S. Role of protein kinase C activation in synthesis of complement components C2 and factor B in interferon-gamma-stimulated human fibroblasts, glioblastoma cell line A172 and monocytes. Biochem J. 1995 Jan 15;305(Pt 2):425–431. doi: 10.1042/bj3050425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wetsel R. A., Lemons R. S., Le Beau M. M., Barnum S. R., Noack D., Tack B. F. Molecular analysis of human complement component C5: localization of the structural gene to chromosome 9. Biochemistry. 1988 Mar 8;27(5):1474–1482. doi: 10.1021/bi00405a012. [DOI] [PubMed] [Google Scholar]
- Whaley K. Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral blood monocytes. J Exp Med. 1980 Mar 1;151(3):501–516. doi: 10.1084/jem.151.3.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whitehead A. S., Solomon E., Chambers S., Bodmer W. F., Povey S., Fey G. Assignment of the structural gene for the third component of human complement to chromosome 19. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5021–5025. doi: 10.1073/pnas.79.16.5021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Bruijn M. H., Fey G. H. Human complement component C3: cDNA coding sequence and derived primary structure. Proc Natl Acad Sci U S A. 1985 Feb;82(3):708–712. doi: 10.1073/pnas.82.3.708. [DOI] [PMC free article] [PubMed] [Google Scholar]



