title: No role of alpha-Gal in human monocyte-endothelial cell interactions in vitro.
abstract: Vascularized organ xenografts undergoing acute vascular rejection (AVR) are infiltrated by innate immune cells such as monocytes/macrophages. Herein, human monocyte static and dynamic adhesion to, and migration across, human and porcine aortic endothelial cells (HAEC and PAEC) were investigated. To elucidate the role of Gal alpha1,3Gal (alpha-Gal) epitopes in these processes in the absence of anti-Gal antibodies (Ab), this determinant was aberrantly expressed in HAEC. HAEC were transduced with a lentiviral vector encoding the porcine alpha1,3 galactosyltransferase to express alpha-Gal at high frequencies (75-95%). Alpha-Gal expression on HAEC did not increase their ability to support monocyte transendothelial migration or adhesion under either static or flow conditions. Porcine and human endothelium supported static adhesion and migration of monocytes equally well. However, human monocytes adhered less to PAEC than to HAEC (P = 0.03) under flow following human, but not porcine, tumour necrosis factor-alpha stimulation. In the absence of anti-Gal Ab, the alpha-Gal epitope does not contribute to increased monocyte adhesion to, or migration across, endothelium. Thus, inhibiting adhesion receptor-ligand interactions essential for the adhesion of human monocytes to porcine endothelium may be more important than carbohydrate remodelling of donor pigs to prevent adhesion/infiltration of monocytes into organ xenografts during AVR.
authors.affiliation: Division of Clinical Immunology F79, Karolinska Institutet, Karolinska University Hospital in Huddinge, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Ehrnfelt
authors.forename: Z
authors.initials: Z
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: Holgersson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004187:Disaccharides / Q000276:immunology / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005700:Galactosyltransferases / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000906:Antibodies; C111835:CCL2 protein, human; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D016895:Culture Media, Serum-Free; D004187:Disaccharides; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C055075:galactosyl-(1-3)galactose; D049452:Green Fluorescent Proteins; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase