ANTIBODIES TO HUMAN ADHESION MOLECULES AND THEIR LIGANDS - CROSS-SPECIES REACTIVITY AND POTENTIAL APPLICATION IN XENOTRANSPLANTATION

Given the renewed interest in the possibility of using animals as an a lternative source of organs for transplantation, it would be useful to have tools to study and manipulate the inflammatory response to a xen ograft. With this in mind, we have screened cynomolgus monkey and porc ine tissue with 37 antibodies specific for human leukocyte differentia tion antigens add adhesion molecules. The cynomolgus monkey, an old wo rld primate, is a concordant species with respect to humans, in contra st to the pig, which is a discordant species. The cross-species reacti vities of the antibodies tested fall into three groups: i) no crossrea ctivity; ii) crossreactivity with a tissue distribution similar to tha t in the human; iii) crossreactivity, but with a distribution differen t from that in the human. Those antibodies directed against E- and P-s electin, ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascul ar cell adhesion molecule-1), which were reactive with monkey tissue, had a similar distribution to that seen in human tissue, but were unre active with the porcine tissue tested. While all anti-CD31 antibody de tected a conserved epitope on endothelium, species differences were ap parent in leukocyte reactivity. One of the antibodies directed against CD18 reacted with leukocytes in all three species, whereas the other antibody detected an epitope present on porcine muscle/connective tiss ue. While antibodies to VLA-4 (Very Late Antigen-4) detected a small n umber of leukocytes in the kidney, they also reacted with the Bowman's capsule in the kidney and matrix protein/connective tissue in the lym ph node. This study indicates that when antibodies react across specie s, some epitopes recognized in the old world nonhuman primates may hav e a distribution similar to those detected in human tissue, whereas in more distant species such as the pig, in many instances the epitope i s present on entirely different structures. Nevertheless, the absence of crossreactivity of human reagents with porcine tissue may allow tar geting of molecules in a species-specific manner, allowing their use f or diagnostic or therapeutic purposes.