Beta1 integrin as a xenoantigen in fetal porcine mesencephalic cells transplanted into the rat brain.
Xenografts of fetal porcine mesencephalic cells implanted into the rat striatum are generally rejected within several weeks. The fetal donor mesencephalon predominantly consists of neurons, but also contains microglial and endothelial cells, which are more immunogenic. In the present work, we investigated the occurrence of donor endothelial cells in grafts of porcine mesencephalic cells implanted into the rat striatum. Pig endothelial cells were monitored by immunochemical methods, using a monoclonal antibody (mAb) that recognizes a peptidic epitope of the porcine beta1 integrin, and isolectin IB4, for the staining of the Galalpha1,3Gal epitope. The analysis also involved the detection of the pig hyaluronate receptor CD44, and the cell adhesion molecule CD31. The anti-beta1 integrin mAb revealed endothelial-like cells in grafts of porcine mesencephalic cells as soon as 1 week after implantation. A similar staining pattern was obtained with the IB4 lectin. Unlike aortic endothelial cells, these pig brain-derived endothelial-like cells were not recognized by the anti-CD44 antibody. They also failed to express the CD31 adhesion molecule, a fact which suggests that they remained poorly mature, even in grafts maintained during 45 days in immunosuppressed rats. Interestingly, a strong expression of beta1 integrin immunoreactivity was noticed in a large proportion (80%) of the cells freshly dissociated from the fetal pig mesencephalic tissue. The immunoreactivity decreased progressively after transplantation of the cells into the rat brain. This observation suggests that dissociated neuroblasts are capable of a temporary expression of beta1 integrin. This molecule is known to participate in the process of cell sorting and migration in the developing brain. Hence, its expression could be the hallmark of a rescue mechanism triggered by the disruption of the cell/matrix interactions during the dissociation of the fetal mesencephalon. This disruption might account for part of the dramatic cell death process that occurs during the manipulation of the donor tissue.
Martin
Caroline
C
Institut National de la Santé et de la Recherche Médicale, Unité 643, Nantes, France.
Melchior
Benoît
B
Nerrière-Daguin
Véronique
V
Naveilhan
Philippe
P
Soulillou
Jean-Paul
JP
Brachet
Philippe
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015478:Antigens, Heterophile / Q000276:immunology* / Q000378:metabolism; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D016380:Brain Tissue Transplantation / Q000276:immunology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation; D016332:Fetal Tissue Transplantation / Q000276:immunology; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000276:immunology* / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology* / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D013552:Swine
D000911:Antibodies, Monoclonal; D015478:Antigens, Heterophile; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D019408:Platelet Endothelial Cell Adhesion Molecule-1