UNIGE document Scientific Article
previous document  unige:20087  next document
add to browser collection
Title

Human leukocyte transmigration across Galalpha(1,3)Gal-negative porcine endothelium is regulated by human CD18 and CD99
Authors
Schneider, Marten K. J.
Ghielmetti, Maddalena
Rhyner, Daniel M.
Antsiferova, Maria A.
Seebach, Jorg Dieter
Published in Transplantation. 2009, vol. 87, no. 4, p. 491-499
Abstract BACKGROUND: In pig-to-human xenotransplantation cross-species receptor interactions mediate cellular infiltration and rejection of porcine grafts. However, the mechanisms responsible for recruitment of human leukocyte subsets across porcine endothelial cells (EC) remain largely unknown. Here, we investigated the role of CD99, CD18, and Galalpha(1,3)Gal (Gal) in this process. METHODS: Adhesion and transmigration of human peripheral blood mononuclear cell (PBMC) subsets on Gal and Gal porcine EC (pEC) and on human EC was analyzed using a two-compartment system separated by a permeable membrane. The mechanisms of human PBMC recruitment to pEC were investigated by blocking cell surface receptors and by differentially measuring adhesion and transendothelial migration (TEM). RESULTS: Blocking of CD18, but not CD99, decreased human PBMC adhesion on pEC, whereas blocking of CD18 or CD99 strongly reduced the subsequent human PBMC TEM across pEC. The inhibitory effect of CD99 blockade was slightly stronger across pEC as compared with human EC. A critical role for Gal in TEM of human monocytes, B, natural killer (NK), NK/T, and T cells was excluded by evaluating TEM across pEC derived from Gal and Gal pigs. CONCLUSIONS: CD99 and CD18, but not Gal, play a critical role in human monocyte and lymphocyte TEM across pEC, and their respective porcine ligands may serve as targets to specifically inhibit human leukocyte recruitment in pig-to-human xenotransplantation.
Keywords Animals — Antigens, CD/*physiology — Antigens, CD18/*physiology — Cell Adhesion — Cell Adhesion Molecules/*physiology — Cell Movement/drug effects/*physiology — Disaccharides/*deficiency/pharmacology — Endothelium, Vascular/*physiology — Graft Rejection/prevention & control — Homeostasis — Humans — Leukocytes/drug effects/*physiology — Swine — Transplantation, Heterologous
Identifiers
PMID: 19307784
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Structures
Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités
Research group Groupe Seebach Jorg Dieter (transplantation et immunologie) (856)
Citation
(ISO format) 		SCHNEIDER, Marten K. J. et al. Human leukocyte transmigration across Galalpha(1,3)Gal-negative porcine endothelium is regulated by human CD18 and CD99. In: Transplantation, 2009, vol. 87, n° 4, p. 491-499. https://archive-ouverte.unige.ch/unige:20087

218 hits

0 download

Contact an author

Update request

Update

Deposited on : 2012-04-23

Export document
Format :
Citation style :