Molecular and functional analysis of porcine E-selectin reveals a potential role in xenograft rejection.
In this study, we report the molecular and functional characterization of porcine E-selectin. Incubation of porcine endothelial cells with human TNF alpha but not human IL-1 resulted in a marked increase in binding to human neutrophils. In order to confirm that this interaction was mediated by E-selectin, we isolated the full-length porcine E-selectin cDNA which contained an open reading frame encoding 485 amino acids with 75% identity to human E-selectin. Expression or recombinant porcine E-selectin in COS cells resulted in surface expression of the protein and increased binding to human neutrophils. Northern blot analysis showed that treatment of porcine endothelial cells with human TNF alpha but not human IL-1 resulted in high levels of porcine E-selectin mRNA. Taken together, our data establish that porcine E-selectin mediates adhesive interactions between porcine endothelial cells and human leukocytes that may contribute to xenograft rejection.
Rollins
S A
SA
Department of Immunobiology, Alexion Pharmaceuticals, Inc., New Haven, CT 06511.
Evans
M J
MJ
Johnson
K K
KK
Elliot
E A
EA
Squinto
S P
SP
Matis
L A
LA
Rother
R P
RP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006084:Graft Rejection; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D013552:Swine; D014158:Transcription, Genetic / Q000187:drug effects; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha