Cross-species compatibility of intercellular adhesion molecule-1 (CD54) with its ligands.
BACKGROUND
The molecular interactions of intercellular adhesion molecule-1 (ICAM-1; CD54) are potentially important in several situations in the context of pig-to-human xenotransplantation. If porcine bone marrow is to be used for the induction of xenograft tolerance in humans, the role that has been suggested for ICAM-1 in the interactions of haematopoietic stem cells makes its cross-species compatibility important. Similarly, the potential role of ICAM-1 interactions in graft rejection makes it an important molecule to study.


METHODS
An in vitro static cell-to-cell adhesion study was used to look at the successful interaction of ICAM-1 with its ligands across the pig-human species barrier in both directions. A second in vitro system, the standard long-term bone marrow culture (LT-BMC), was used to study the functional role of ICAM-1 in haematopoiesis.


RESULTS
Human ICAM-1 was able to adhere to ligands on porcine cells, including one or more ligand that contains CD18. Conversely, human CD18-containing ligands mediated adherence to porcine cells. Using the long-term bone marrow culture system, there was no evidence that blocking the interactions of ICAM-1 inhibited hematopoiesis, either in the human-human or pig-human combinations of precursor cells and marrow stroma.


CONCLUSIONS
ICAM-1 is able to interact with at least some of its ligands across the species barrier, in both pig-human and human-pig combinations. However, the interactions of ICAM-1 do not appear to be central to hematopoiesis, at least in the model system used.
Warrens
A N
AN
Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
Simon
A R
AR
Theodore
P R
PR
Sachs
D H
DH
Sykes
M
M
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D003429:Cross Reactions; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D016377:Organ Transplantation; D013045:Species Specificity; D013552:Swine; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
D008024:Ligands; D018799:Intercellular Adhesion Molecule-1