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Human natural antibodies cytotoxic to pig embryonic brain cells recognize novel non-Galalpha1,3Gal-based xenoantigens

Sumitran-Holgersson, S; Liu, J; Czech, Kimberly A; Christensson, B; Widner, H LU and Holgersson, J. (1999) In Experimental Neurology 159(2). p.61-347
Abstract

Transplantation of porcine embryonic brain cells, including dopaminergic neurons, from ventral mesencephalon (VM) is considered a potential treatment for patients with Parkinson's disease. In the present study, we characterized the distribution among VM cells of the major porcine endothelial xenoantigen, the Galalpha1,3Gal epitope, and evaluated the cytotoxic effect of anti-Galalpha1,3Gal antibody-depleted and nondepleted human AB serum on VM cells. Overall levels of Galalpha1,3Gal-epitope expression was very low on the VM cell population using Bandeiraea simplicifolia IB(4) lectin staining of resuspended VM cells in flow cytometric analyses or staining of SDS-PAGE-separated, solubilized VM cell membrane proteins in Western blot... (More)

Transplantation of porcine embryonic brain cells, including dopaminergic neurons, from ventral mesencephalon (VM) is considered a potential treatment for patients with Parkinson's disease. In the present study, we characterized the distribution among VM cells of the major porcine endothelial xenoantigen, the Galalpha1,3Gal epitope, and evaluated the cytotoxic effect of anti-Galalpha1,3Gal antibody-depleted and nondepleted human AB serum on VM cells. Overall levels of Galalpha1,3Gal-epitope expression was very low on the VM cell population using Bandeiraea simplicifolia IB(4) lectin staining of resuspended VM cells in flow cytometric analyses or staining of SDS-PAGE-separated, solubilized VM cell membrane proteins in Western blot analyses. Lectin-histochemical staining of sections of pig embryonal VM regions with BSA IB(4) lectin showed staining restricted to endothelial cells and microglia. In the presence of complement, both nondepleted and anti-Galalpha1,3Gal antibody-depleted AB sera were shown to be cytotoxic to VM cells as assessed in microcytotoxicity- and flow cytometry-based cytotoxicity assays. Purified IgM and IgG were both cytotoxic in the presence of complement. Three major VM cell membrane antigens of approximately 210, 105, and 50 kDa were reactive with natural IgM antibodies present in pooled human AB sera. Thus, antibody-dependent cytotoxicity may contribute to pig to human brain cell xenorejection, necessitating donor tissue modifications prior to a more widespread utilization of neural tissue xenografting.

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published
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keywords
ABO Blood-Group System, Animals, Antigens, Heterophile, Aorta, Brain, Cytotoxicity, Immunologic, Disaccharides, Embryo, Mammalian, Endothelium, Vascular, Epitopes, Humans, Immunoglobulin G, Immunoglobulin M, Mesencephalon, Neurons, Swine
in
Experimental Neurology
volume
159
issue
2
pages
15 pages
publisher
Academic Press
external identifiers
  • scopus:0032847930
ISSN
0014-4886
DOI
10.1006/exnr.1999.7181
language
English
LU publication?
yes
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36c499e6-aa80-4ee1-ab89-97342b21e02e
date added to LUP
2017-04-19 18:22:47
date last changed
2017-10-01 05:33:20
@article{36c499e6-aa80-4ee1-ab89-97342b21e02e,
  abstract     = {<p>Transplantation of porcine embryonic brain cells, including dopaminergic neurons, from ventral mesencephalon (VM) is considered a potential treatment for patients with Parkinson's disease. In the present study, we characterized the distribution among VM cells of the major porcine endothelial xenoantigen, the Galalpha1,3Gal epitope, and evaluated the cytotoxic effect of anti-Galalpha1,3Gal antibody-depleted and nondepleted human AB serum on VM cells. Overall levels of Galalpha1,3Gal-epitope expression was very low on the VM cell population using Bandeiraea simplicifolia IB(4) lectin staining of resuspended VM cells in flow cytometric analyses or staining of SDS-PAGE-separated, solubilized VM cell membrane proteins in Western blot analyses. Lectin-histochemical staining of sections of pig embryonal VM regions with BSA IB(4) lectin showed staining restricted to endothelial cells and microglia. In the presence of complement, both nondepleted and anti-Galalpha1,3Gal antibody-depleted AB sera were shown to be cytotoxic to VM cells as assessed in microcytotoxicity- and flow cytometry-based cytotoxicity assays. Purified IgM and IgG were both cytotoxic in the presence of complement. Three major VM cell membrane antigens of approximately 210, 105, and 50 kDa were reactive with natural IgM antibodies present in pooled human AB sera. Thus, antibody-dependent cytotoxicity may contribute to pig to human brain cell xenorejection, necessitating donor tissue modifications prior to a more widespread utilization of neural tissue xenografting.</p>},
  author       = {Sumitran-Holgersson, S and Liu, J and Czech, Kimberly A and Christensson, B and Widner, H and Holgersson, J.},
  issn         = {0014-4886},
  keyword      = {ABO Blood-Group System,Animals,Antigens, Heterophile,Aorta,Brain,Cytotoxicity, Immunologic,Disaccharides,Embryo, Mammalian,Endothelium, Vascular,Epitopes,Humans,Immunoglobulin G,Immunoglobulin M,Mesencephalon,Neurons,Swine},
  language     = {eng},
  number       = {2},
  pages        = {61--347},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Human natural antibodies cytotoxic to pig embryonic brain cells recognize novel non-Galalpha1,3Gal-based xenoantigens},
  url          = {http://dx.doi.org/10.1006/exnr.1999.7181},
  volume       = {159},
  year         = {1999},
}