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 alternative source of organs for transplantation, it would be useful to have tools to study and manipulate the inflammatory response to a xenograft. With this in mind, we have screened cynomolgus monkey and porcine tissue with 37 antibodies specific for human leukocyte differentiation antigens add adhesion molecules. The cynomolgus monkey, an old world primate, is a concordant species with respect to humans, in contrast to the pig, which is a discordant species. The cross-species reactivities of the antibodies tested fall into three groups: i) no crossreactivity; ii) crossreactivity with a tissue distribution similar to that in the human; iii) crossreactivity, but with a distribution different from that in the human. Those antibodies directed against E- and P-selectin, ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1), which were reactive with monkey tissue, had a similar distribution to that seen in human tissue, but were unreactive with the porcine tissue tested. While all anti-CD31 antibody detected a conserved epitope on endothelium, species differences were apparent 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 tissue. While antibodies to VLA-4 (Very Late Antigen-4) detected a small number of leukocytes in the kidney, they also reacted with the Bowman's capsule in the kidney and matrix protein/connective tissue in the lymph node. This study indicates that when antibodies react across species, some epitopes recognized in the old world nonhuman primates may have a distribution similar to those detected in human tissue, whereas in more distant species such as the pig, in many instances the epitope is present on entirely different structures. Nevertheless, the absence of crossreactivity of human reagents with porcine tissue may allow targeting of molecules in a species-specific manner, allowing their use for diagnostic or therapeutic purposes.