International Immunology, Vol 9, 869-876, Copyright © 1997 by Oxford University Press
K Toyomura, T Fujimura, H Murakami, T Natsume, T Shigehisa, N Inoue, J Takeda and T Kinoshita
Organs of transgenic pigs that express human complement regulatory proteins
are under assessment as an alternative to transplantation. A major barrier
to the transplantation of pig organs is the hyperacute rejection caused by
pre-existing antibodies and complement. Pig cells are very susceptible to
human complement, presumably because pig cell- surface complement
regulatory proteins are inefficient against it. Expression of human
complement regulatory proteins, such as decay- accelerating factor and
membrane cofactor proteins (MCP or CD46), by means of transgenes would
confer resistance to human complement upon pig cells, thereby preventing
hyperacute rejection. To express sufficient levels of human complement
regulatory proteins at appropriate sites, regulatory elements of genes of
pig membrane-bound complement regulatory proteins would be useful. To
obtain their cDNAs, we transfected human cells with a pig cDNA library,
selected cells by incubation with pig complement and rescued the plasmids.
We cloned a cDNA for the pig homologue of MCP, pMCP. The cDNA encoded a
predicted protein of 363 amino acids with 42% amino acid identity with
human MCP. The pMCP consisted of four short consensus repeats, a
Ser/Thr/Pro-rich domain, and transmembrane and cytoplasmic domains.
Recombinant soluble pMCP that lacked transmembrane and cytoplasmic domains
had factor I cofactor activity in C3b cleavage, indicating that it is
functionally, as well as structurally homologous to MCP. FACS analysis with
anti-pMCP mAb demonstrated that pMCP is expressed on all blood leukocytes,
erythrocytes, and on endothelial and epithelial cell lines.
ARTICLES
Molecular cloning of a pig homologue of membrane cofactor protein (CD46)
Research and Development Center, Nippon Meat Packers Inc., Ibaraki, Japan.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. E. Suter, M. B. Chein, V. von Messling, B. Yip, R. Cattaneo, W. Vernau, B. R. Madewell, and C. A. London In vitro Canine Distemper Virus Infection of Canine Lymphoid Cells: A Prelude to Oncolytic Therapy for Lymphoma Clin. Cancer Res., February 15, 2005; 11(4): 1579 - 1587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Schneider-Schaulies, M. J. Martin, J. S. Logan, R. Firsching, V. ter Meulen, and L. E. Diamond CD46 transgene expression in pig peripheral blood mononuclear cells does not alter their susceptibility to measles virus or their capacity to downregulate endogenous and transgenic CD46 J. Gen. Virol., June 1, 2000; 81(6): 1431 - 1438. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. K. Liszewski, M. K. Leung, and J. P. Atkinson Membrane Cofactor Protein: Importance of N- and O-Glycosylation for Complement Regulatory Function J. Immunol., October 1, 1998; 161(7): 3711 - 3718. [Abstract] [Full Text] [PDF]
|
|