Distribution of the major xenoantigen (gal (alpha 1-3)gal) for pig to human xenografts

Abstract

We have previously demonstrated that the major epitope in pig tissues detected by naturally occurring human IgM antibodies is galactose (alpha 1-3)galactose. Subsequent biochemical studies demonstrated this epitope to be present on molecules (Mr40-220kDa) on both endothelial cells and lymphocytes. The objective of the present study was to define the distribution of gal(alpha 1-3)gal in different pig tissues, concentrating on those of relevance for the potential transplantation of pig organs or tissues to humans. Adult pig tissues were obtained fresh, fixed, and stained by the immunoperoxidase technique using biotinylated Griffonia simplicifolia lectin (IB4) which binds only to gal(alpha 1-3)gal, and examined histologically. Endothelial cells in all small vessels (capillaries, arterioles and venules) had a unifrom and dense expression of gal(alpha 1-3)gal; in larger vessels, like the aorta, they were less reactive. The highest concentrations were found in the liver parenchyma which stained uniformly, and in the kidney, where the highest amounts were found in the brush border of the proximal convoluted tubules. There was no staining of collecting ducts or glomeruli (except for endothelium) and moderate staining of the distal convoluted tubules. Heart muscle was nonreactive, although the high density of capillaries indicated a reasonable content of gal(alpha 1-3)gal. In contrast to these tissues was the distribution in the pancreas, which, apart from vessels and the lining of ducts, was nonreactive, i.e. islet cells were essentially lacking in gal(alpha 1-3)gal. Other tissues such as the lung contained moderate amounts of material lining the alveoli and bronchioles.(ABSTRACT TRUNCATED AT 250 WORDS)