TISSUE EXPRESSION OF HUMAN-COMPLEMENT INHIBITOR, DECAY-ACCELERATING FACTOR, IN TRANSGENIC PIGS - A POTENTIAL APPROACH FOR PREVENTING XENOGRAFT REJECTION

Since complement-mediated hyperacute rejection of xenografts prevents the use of pigs as organ donors to man, the development of transgenic animals expressing species-specific complement inhibitors could provid e a strategy for overcoming hyperacute rejection, The complement inhib itor, human decay-accelerating factor (hDAF), prevents the assembly of C3 and C5 convertases. In this article, the first histologic analysis of hDAF expression in pig tissues, specifically expression in endothe lial cells of pigs transgenic for hDAF, is described, Twenty-seven tra nsgenic pigs were categorized into 4 groups based on the expression pa tterns in endothelial, vascular smooth muscle, and squamous epithelial cells of skin biopsy specimens, Skin biopsy specimens permitted evalu ation of the pigs without the need to kill them or to perform invasive procedures. Sixteen cases demonstrated endothelial cell staining, Com plete necropsy evaluation, available in 14 of the 27 pigs, correlated with the skin biopsy specimen expression of hDAF, The immunoperoxidase data matched identically with the presence of the mRNA transcript in 25 of the 26 cases where RNA data were available, Also, the staining p atterns of 6 transgenic pig founders and their 9 offspring (total of 9 founder-offspring pairs) correlated, Since transgenes are variably ex pressed in different cell types and since tissue lysates represent a m elange of cell types, histologic evaluation for protein expression in tissues from transgenic animals will be critical if they are to be bre d to become clinical organ donors, In addition to endothelial expressi on of hDAF, its expression on vascular smooth muscle cells may be impo rtant in preventing tissue damage when breaks in the endothelium occur .