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 provide a strategy for overcoming hyperacute rejection. The complement inhibitor, 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 endothelial cells of pigs transgenic for hDAF, is described. Twenty-seven transgenic pigs were categorized into 4 groups based on the expression patterns in endothelial, vascular smooth muscle, and squamous epithelial cells of skin biopsy specimens. Skin biopsy specimens permitted evaluation of the pigs without the need to kill them or to perform invasive procedures. Sixteen cases demonstrated endothelial cell staining. Complete 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 patterns of 6 transgenic pig founders and their 9 offspring (total of 9 founder-offspring pairs) correlated. Since transgenes are variably expressed in different cell types and since tissue lysates represent a melange of cell types, histologic evaluation for protein expression in tissues from transgenic animals will be critical if they are to be bred to become clinical organ donors. In addition to endothelial expression of hDAF, its expression on vascular smooth muscle cells may be important in preventing tissue damage when breaks in the endothelium occur.
Rosengard
A M
AM
Department of Surgery, University of Cambridge, United Kingdom.
Cary
N R
NR
Langford
G A
GA
Tucker
A W
AW
Wallwork
J
J
White
D J
DJ
D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics; D018958:CD55 Antigens; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000378:metabolism*; D013552:Swine
D015703:Antigens, CD; D018958:CD55 Antigens; D008562:Membrane Glycoproteins; D012333:RNA, Messenger