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Expression of human decay accelerating factor or membrane cofactor protein genes on mouse cells inhibits lysis by
D J White1, T Oglesby, M K Liszewski
1Clinical School of Medicine, University of Cambridge Addenbrooke's Hospital, Hills Rd., Cambridge CB2 2QQ.
Abstract:
Mouse cells expressing the human complement regulatory proteins decay accelerating factor (DAF) or membrane cofactor protein (MCP) were produced both by hybridoma technology and by transfection with the appropriate cDNAs. The expression of either or both of these products protected the mouse cell from lysis by human (though not rabbit) complement in the presence of naturally occurring human anti-mouse antibody. This effect could be abrogated by the addition of monoclonal antibody against DAF or MCP. These data suggested that the production of animals transgenic for human complement regulatory proteins should in principle be similarly protected from hyperacute xenograft rejection.
Insights
Mouse cells expressing human complement proteins DAF or MCP were protected from lysis by human complement. This suggests transgenic animals could be protected from hyperacute xenograft rejection.
Area of Science:
- Immunology
- Transplantation Biology
Background:
- Hyperacute xenograft rejection is a major barrier in organ transplantation.
- The complement system plays a critical role in xenograft rejection.
Purpose of the Study:
- To investigate the protective effects of human complement regulatory proteins (DAF and MCP) on mouse cells against human complement-mediated lysis.
- To assess the potential of these proteins in preventing hyperacute xenograft rejection.
Main Methods:
- Production of mouse cells expressing human decay accelerating factor (DAF) or membrane cofactor protein (MCP) using hybridoma technology and cDNA transfection.
- Assessment of cell lysis by human complement in the presence of anti-mouse antibody.
- Abrogation of protective effects using monoclonal antibodies against DAF and MCP.
Main Results:
- Mouse cells expressing either DAF or MCP, or both, were protected from lysis by human complement.
- Protection was observed in the presence of human anti-mouse antibody but not rabbit complement.
- The protective effect was reversed by monoclonal antibodies targeting DAF or MCP.
Conclusions:
- Expression of human DAF or MCP confers resistance to human complement-mediated lysis in mouse cells.
- These findings support the principle that transgenic animals expressing human complement regulatory proteins could be protected from hyperacute xenograft rejection.