Complement-mediated tumor cell damage induced by antibodies against membrane cofactor protein (MCP, CD46)

doi:10.1084/jem.172.6.1673

This Article

	Full Text (PDF, 849K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Seya, T.
	Articles by Akedo, H.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Seya, T.
	Articles by Akedo, H.


Social Bookmarking

	What's this?

ARTICLES

Complement-mediated tumor cell damage induced by antibodies against membrane cofactor protein (MCP, CD46)

T Seya, T Hara, M Matsumoto, Y Sugita and H Akedo
Department of Immunology, Center for Adult Diseases Osaka, Japan.

We have developed polyclonal and monoclonal antibodies against human membrane cofactor protein (MCP) to use as tools to investigate the functions of MCP on intact nucleated cells. Two human T cell lines, CEM and TALL, are CR1- and DAF-. Pretreatment of these cell lines with M177 and polyclonal anti-MCP, which inhibit cofactor activity almost completely, resulted in effective C3 deposition immediately following addition of these cells to Mg2+/EGTA/human sera. The deposited C3 remained expressed partly on the cell surface and most of them were gradually converted to C3bi. Some of the deposited C3 were complexed with membrane proteins, since 140- and 250-kD bands became significantly accumulated on SDS-PAGE by treatment with the antibodies. We next tested whether these C3-coated cells were damaged by complement- mediated cytolysis. p18, an inhibitor of membrane attack complex (MAC) formation, was negative in TALL but positive in CEM. TALL was lysed efficiently only by treatment with the polyclonal anti-MCP, while CEM showed only slight lysis with the same treatment. Monoclonal antibodies to MCP, including M177, caused only minimal cell destruction. Based on these results, together with the fact that decay-accelerating factor (DAF) serves as a factor for preventing C3 attack on human cells, we conclude that MCP and DAF cooperatively protect host cells from C3 targeting and, in these T cell lines, MCP is sufficient for preventing C3 deposition even without DAF. After all, human cells undergo almost no autologous complement-mediated cytolysis if they express at least one of the functionally active inhibitors, MCP, DAF, or p18.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Johnson, J. B., Grant, K., Parks, G. D. (2009). The Paramyxoviruses Simian Virus 5 and Mumps Virus Recruit Host Cell CD46 To Evade Complement-Mediated Neutralization. J. Virol. 83: 7602-7611 [Abstract] [Full Text]
Iacobelli-Martinez, M., Nepomuceno, R. R., Connolly, J., Nemerow, G. R. (2005). CD46-Utilizing Adenoviruses Inhibit C/EBP{beta}-Dependent Expression of Proinflammatory Cytokines. J. Virol. 79: 11259-11268 [Abstract] [Full Text]
Madjd, Z., Durrant, L. G., Bradley, R., Spendlove, I., Ellis, I. O., Pinder, S. E. (2004). Loss of CD55 Is Associated with Aggressive Breast Tumors. Clin. Cancer Res. 10: 2797-2803 [Abstract] [Full Text]
Crimeen-Irwin, B., Ellis, S., Christiansen, D., Ludford-Menting, M. J., Milland, J., Lanteri, M., Loveland, B. E., Gerlier, D., Russell, S. M. (2003). Ligand Binding Determines Whether CD46 Is Internalized by Clathrin-coated Pits or Macropinocytosis. J. Biol. Chem. 278: 46927-46937 [Abstract] [Full Text]
Mori, Y., Seya, T., Huang, H. L., Akkapaiboon, P., Dhepakson, P., Yamanishi, K. (2002). Human Herpesvirus 6 Variant A but Not Variant B Induces Fusion from Without in a Variety of Human Cells through a Human Herpesvirus 6 Entry Receptor, CD46. J. Virol. 76: 6750-6761 [Abstract] [Full Text]
Kurita-Taniguchi, M., Fukui, A., Hazeki, K., Hirano, A., Tsuji, S., Matsumoto, M., Watanabe, M., Ueda, S., Seya, T. (2000). Functional Modulation of Human Macrophages Through CD46 (Measles Virus Receptor): Production of IL-12 p40 and Nitric Oxide in Association with Recruitment of Protein-Tyrosine Phosphatase SHP-1 to CD46. J. Immunol. 165: 5143-5152 [Abstract] [Full Text]
Chen, S., Caragine, T., Cheung, N.-K. V., Tomlinson, S. (2000). Surface Antigen Expression and Complement Susceptibility of Differentiated Neuroblastoma Clones. Am. J. Pathol. 156: 1085-1091 [Abstract] [Full Text]
Iwata, K., Seya, T., Yanagi, Y., Pesando, J. M., Johnson, P. M., Okabe, M., Ueda, S., Ariga, H., Nagasawa, S. (1995). Diversity of Sites for Measles Virus Binding and for Inactivation of Complement C3b and C4b on Membrane Cofactor Protein CD46. J. Biol. Chem. 270: 15148-15152 [Abstract] [Full Text]