Distribution of membrane cofactor protein (MCP/CD46) on pig tissues. Relevance to xenotransplantation

Membrane cofactor protein (MCP; CD46) is a 50-60 000 MW glycoprotein, expre ssed on a wide variety of cells and tissues in man, which plays an importan t role in regulating complement activation. Human MCP has also been shown t o be the receptor for measles virus. We have recently identified the pig an alogue of MCP and demonstrated that pig MCP has cofactor activity for facto r I-mediated cleavage of C3b when these components are derived either from pig or human. As a consequence, pig MCP is an efficient regulator of the cl assic and alternative pathways of human and pig complement. In order to def ine the potential importance of MCP in protecting against complement activa tion in the pig, we have conducted a comprehensive survey of its distributi on in pig cells and organs. As in humans, MCP in the pig is broadly and abu ndantly distributed. Pig MCP is highly expressed on all circulating cells, including erythrocytes, in contrast to its absence on human erythrocytes. M ultiple isoforms of MCP are found on cells and in tissues, probably represe nting products of alternative splicing analogous to those found in man. MCP is abundantly expressed throughout all tissues examined with particularly strong staining on the vascular endothelium. Connective tissue elements wit hin liver and testis are also strongly stained by anti-pig MCP antibodies. Pig MCP is expressed only weakly on skeletal muscle cells and expression is absent from smooth muscle cells in the lung and vessel walls, sites at whi ch human MCP is expressed. Of particular note, MCP is not expressed in B-ce ll areas of the germinal centres of lymph nodes.