Porcine endothelium supports transendothelial migration of human leukocytesubpopulations: Antiporcine vascular cell adhesion molecule antibodies as species-specific blockers of transendothelial monocyte and natural killer cell migration

Background In cases where hyperacute rejection has been prevented, pig to p rimate organ transplantation results in a delayed rejection mediated by gra ft-infiltrating leukocytes, The migration of human leukocytes across porcin e endothelium is poorly characterized, but may offer targets for species-sp ecific antirejection therapy, Methods. Transwell tissue culture inserts with endothelial cells growing on polycarbonate filters were used to characterize the migration of periphera l blood monocuclear cells and purified leukocyte subpopulations across pig and human endothelial cells and cell lines. Endothelial cell morphology was evaluated by scanning and transmission electron microscopy, and the contri bution of different adhesion receptor pairs to transendothelial migration w as evaluated by antibody blocking experiments, Results, There were no evident quantitative or qualitative differences in t he capacity of human and porcine endothelium to support transendothelial mi gration of human leukocytes [T, B, and natural killer (NK) cells, monocytes , and neutrophils], Monocytes and large granular CD3(+) lymphocytes migrate d most efficiently across the endothelium, Antiporcine vascular cell adhesi on molecule-1 antibodies blocked transendothelial migration of human monocy tes and Mt cells across tumor necrosis factor-alpha stimulated pig endothel ium by at least 60%. Anti-CD18 antibodies had no effect on the migration of human NK cells across pig endothelium, whereas they partly blocked migrati on of NK cells across human endothelium and migration of monocytes across p orcine endothelium, Interleukin-2 stimulated, but not unstimulated, T and N K cells were cytotoxic to porcine endothelium, Conclusions. Porcine endothelium supports transendothelial migration of hum an leukocyte subpopulations as efficiently as human endothelium, Incompatib ilities in some adhesion receptor pairs may be compensated for by other adh esion receptor pairs, as exemplified by human NK cells whose migration acro ss human, but not pig, endothelium was blocked by anti-CD18 antibodies. Ant iporcine vascular cell adhesion molecule-1 antibodies may be used as specie s-specific blockers of transendothelial NK cell and monocyte migration, and as such may prove to be useful inhibitors of cellular organ xenograft reje ction.