Abstract
The monoclonal antibody 5I2 recognizes and functionally inhibits a Crry-like complement regulator molecule on rat cells (corresponding to human decay accelerating factor and membrane cofactor protein activity). The inhibition of complement regulatory activity by 5I2 antibody results in complement deposition on rat cell membranes exposed to homologous complement. Two subclones of KDH-8 rat hepatoma were selected for the experiments; one expressing high (CrryH) and the second low (CrryL) amounts of Crry-like antigen. Both sublines grow in vivo in syngeneic rats, but at lower cell doses (< 10(5) cells/rat) the survival time of rats injected with CrryL cells is prolonged. Injection of tumour-bearing rats with 5I2 monoclonal antibody intraperitoneally did not influence the tumour growth. However, it resulted in 50% mortality within a few hours, accompanied by severe haemorrhage in the peritoneal cavity. Pretreatment of the tumour cells with 5I2 monoclonal antibody or its F(ab')2 fragment substantially increased the survival time of recipient rats. Even permanent survivors were found, indicating that cell membrane-associated complement regulatory activity, which provides protection against attack of homologous complement, is necessary for in vivo tumour growth.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bara S., Lint T. F. The third component of complement (C3) bound to tumor target cells enhances their sensitivity to killing by activated macrophages. J Immunol. 1987 Feb 15;138(4):1303–1309. [PubMed] [Google Scholar]
- Budzko D. B., Lachmann P. J., McConnell I. Activation of the alternative complement pathway by lymphoblastoid cell lines derived from patients with Burkitt's lymphoma and infectious mononucleosis. Cell Immunol. 1976 Mar 1;22(1):98–109. doi: 10.1016/0008-8749(76)90011-3. [DOI] [PubMed] [Google Scholar]
- Cassatella M. A., Bazzoni F., Ceska M., Ferro I., Baggiolini M., Berton G. IL-8 production by human polymorphonuclear leukocytes. The chemoattractant formyl-methionyl-leucyl-phenylalanine induces the gene expression and release of IL-8 through a pertussis toxin-sensitive pathway. J Immunol. 1992 May 15;148(10):3216–3220. [PubMed] [Google Scholar]
- Collins P. D., Jose P. J., Williams T. J. The sequential generation of neutrophil chemoattractant proteins in acute inflammation in the rabbit in vivo. Relationship between C5a and proteins with the characteristics of IL-8/neutrophil-activating protein 1. J Immunol. 1991 Jan 15;146(2):677–684. [PubMed] [Google Scholar]
- Dinarello C. A. Dissociation of transcription from translation of human IL-1 beta: induction of steady state mRNA by adherence or recombinant C5a in the absence of translation. Proc Soc Exp Biol Med. 1992 Jun;200(2):228–232. doi: 10.3181/00379727-200-43425. [DOI] [PubMed] [Google Scholar]
- Funabashi K., Okada N., Matsuo S., Yamamoto T., Morgan B. P., Okada H. Tissue distribution of complement regulatory membrane proteins in rats. Immunology. 1994 Mar;81(3):444–451. [PMC free article] [PubMed] [Google Scholar]
- Harada R., Okada N., Fujita T., Okada H. Purification of 1F5 antigen that prevents complement attack on homologous cell membranes. J Immunol. 1990 Mar 1;144(5):1823–1828. [PubMed] [Google Scholar]
- Hourcade D., Holers V. M., Atkinson J. P. The regulators of complement activation (RCA) gene cluster. Adv Immunol. 1989;45:381–416. doi: 10.1016/s0065-2776(08)60697-5. [DOI] [PubMed] [Google Scholar]
- Hughes T. R., Piddlesden S. J., Williams J. D., Harrison R. A., Morgan B. P. Isolation and characterization of a membrane protein from rat erythrocytes which inhibits lysis by the membrane attack complex of rat complement. Biochem J. 1992 May 15;284(Pt 1):169–176. doi: 10.1042/bj2840169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hughes T. R., Piddlesden S. J., Williams J. D., Harrison R. A., Morgan B. P. Isolation and characterization of a membrane protein from rat erythrocytes which inhibits lysis by the membrane attack complex of rat complement. Biochem J. 1992 May 15;284(Pt 1):169–176. doi: 10.1042/bj2840169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jose P. J., Collins P. D., Perkins J. A., Beaubien B. C., Totty N. F., Waterfield M. D., Hsuan J., Williams T. J. Identification of a second neutrophil-chemoattractant cytokine generated during an inflammatory reaction in the rabbit peritoneal cavity in vivo. Purification, partial amino acid sequence and structural relationship to melanoma-growth-stimulatory activity. Biochem J. 1991 Sep 1;278(Pt 2):493–497. doi: 10.1042/bj2780493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kameyoshi Y., Matsushita M., Okada H. Murine membrane inhibitor of complement which accelerates decay of human C3 convertase. Immunology. 1989 Dec;68(4):439–444. [PMC free article] [PubMed] [Google Scholar]
- Kinoshita T., Lavoie S., Nussenzweig V. Regulatory proteins for the activated third and fourth components of complement (C3b and C4b) in mice. II. Identification and properties of complement receptor type 1 (CR1). J Immunol. 1985 Apr;134(4):2564–2570. [PubMed] [Google Scholar]
- Kuraya M., Yefenof E., Klein G., Klein E. Expression of the complement regulatory proteins CD21, CD55 and CD59 on Burkitt lymphoma lines: their role in sensitivity to human serum-mediated lysis. Eur J Immunol. 1992 Jul;22(7):1871–1876. doi: 10.1002/eji.1830220729. [DOI] [PubMed] [Google Scholar]
- Lachmann P. J. The control of homologous lysis. Immunol Today. 1991 Sep;12(9):312–315. doi: 10.1016/0167-5699(91)90005-E. [DOI] [PubMed] [Google Scholar]
- Liszewski M. K., Post T. W., Atkinson J. P. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol. 1991;9:431–455. doi: 10.1146/annurev.iy.09.040191.002243. [DOI] [PubMed] [Google Scholar]
- Meri S., Morgan B. P., Davies A., Daniels R. H., Olavesen M. G., Waldmann H., Lachmann P. J. Human protectin (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers. Immunology. 1990 Sep;71(1):1–9. [PMC free article] [PubMed] [Google Scholar]
- Morgan E. L., Sanderson S., Scholz W., Noonan D. J., Weigle W. O., Hugli T. E. Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis. J Immunol. 1992 Jun 15;148(12):3937–3942. [PubMed] [Google Scholar]
- Mrowietz U., Schröder J. M., Brasch J., Christophers E. Infiltrating neutrophils differ from circulating neutrophils when stimulated with C5a, NAP-1/IL-8, LTB4 and FMLP. Scand J Immunol. 1992 Jan;35(1):71–78. doi: 10.1111/j.1365-3083.1992.tb02835.x. [DOI] [PubMed] [Google Scholar]
- Nicholson-Weller A., Burge J., Austen K. F. Purification from guinea pig erythrocyte stroma of a decay-accelerating factor for the classical c3 convertase, C4b,2a. J Immunol. 1981 Nov;127(5):2035–2039. [PubMed] [Google Scholar]
- Paul M. S., Aegerter M., O'Brien S. E., Kurtz C. B., Weis J. H. The murine complement receptor gene family. Analysis of mCRY gene products and their homology to human CR1. J Immunol. 1989 Jan 15;142(2):582–589. [PubMed] [Google Scholar]
- Ramos O. F., Kai C., Yefenof E., Klein E. The elevated natural killer sensitivity of targets carrying surface-attached C3 fragments require the availability of the iC3b receptor (CR3) on the effectors. J Immunol. 1988 Feb 15;140(4):1239–1243. [PubMed] [Google Scholar]
- Ramos O. F., Sármay G., Klein E., Yefenof E., Gergely J. Complement-dependent cellular cytotoxicity: lymphoblastoid lines that activate complement component 3 (C3) and express C3 receptors have increased sensitivity to lymphocyte-mediated lysis in the presence of fresh human serum. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5470–5474. doi: 10.1073/pnas.82.16.5470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rollins S. A., Sims P. J. The complement-inhibitory activity of CD59 resides in its capacity to block incorporation of C9 into membrane C5b-9. J Immunol. 1990 May 1;144(9):3478–3483. [PubMed] [Google Scholar]
- Sakurada C., Seno H., Dohi N., Takizawa H., Nonaka M., Okada N., Okada H. Molecular cloning of the rat complement regulatory protein, 5I2 antigen. Biochem Biophys Res Commun. 1994 Feb 15;198(3):819–826. doi: 10.1006/bbrc.1994.1117. [DOI] [PubMed] [Google Scholar]
- Schindler R., Gelfand J. A., Dinarello C. A. Recombinant C5a stimulates transcription rather than translation of interleukin-1 (IL-1) and tumor necrosis factor: translational signal provided by lipopolysaccharide or IL-1 itself. Blood. 1990 Oct 15;76(8):1631–1638. [PubMed] [Google Scholar]
- Seya T., Hara T., Matsumoto M., Akedo H. Quantitative analysis of membrane cofactor protein (MCP) of complement. High expression of MCP on human leukemia cell lines, which is down-regulated during cell differentiation. J Immunol. 1990 Jul 1;145(1):238–245. [PubMed] [Google Scholar]
- Seya T., Hara T., Matsumoto M., Sugita Y., Akedo H. Complement-mediated tumor cell damage induced by antibodies against membrane cofactor protein (MCP, CD46). J Exp Med. 1990 Dec 1;172(6):1673–1680. doi: 10.1084/jem.172.6.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sugita Y., Nakano Y., Tomita M. Isolation from human erythrocytes of a new membrane protein which inhibits the formation of complement transmembrane channels. J Biochem. 1988 Oct;104(4):633–637. doi: 10.1093/oxfordjournals.jbchem.a122524. [DOI] [PubMed] [Google Scholar]
- Sugiura C., Itaya T., Kondoh N., Oikawa T., Kuzumaki N., Takeichi N., Hosokawa M., Kobayashi H. Xenogenization of tumor cells by transfection with plasmid containing env gene of Friend leukemia virus. Jpn J Cancer Res. 1988 Dec;79(12):1259–1263. doi: 10.1111/j.1349-7006.1988.tb01553.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takizawa H., Okada N., Okada H. Complement inhibitor of rat cell membrane resembling mouse Crry/p65. J Immunol. 1994 Mar 15;152(6):3032–3038. [PubMed] [Google Scholar]
- Terachi T., Stanescu G., Pontes J. E., Medof M. E., Caulfield M. J. Coexistence of autologous antibodies and decay-accelerating factor, an inhibitor of complement, on human renal tumor cells. Cancer Res. 1991 May 15;51(10):2521–2523. [PubMed] [Google Scholar]
