Publication Date:
1998-09-22
Description:
The major barrier to transplantation across discordant species, such as from pig to human, is rejection mediated by xenoreactive natural antibodies (XNA) that bind the carbohydrate epitope Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal) on donor tissues. This epitope is synthesized by the enzyme glucosyltransferase uridine 5'-diphosphate galactose:beta-D-galactosyl-1, 4-N-acetyl-D-glucosaminide alpha(1-3)galactosyltransferase (E.C. 2.4.1.151), or simply alphaGT. When a functional alphaGT gene was introduced by retroviral gene transfer into bone marrow cells, alphaGal XNA production in a murine model ceased. Thus, genetic engineering of bone marrow may overcome humoral rejection of discordant xenografts and may be useful for inducing B cell tolerance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bracy, J L -- Sachs, D H -- Iacomini, J -- New York, N.Y. -- Science. 1998 Sep 18;281(5384):1845-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular and Molecular Biology Program, Allegheny University of the Health Sciences, 2900 Queen Lane, Philadelphia, PA 19129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9743496" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Antibody Formation
;
B-Lymphocytes/immunology
;
Bone Marrow Cells/*enzymology
;
Bone Marrow Transplantation
;
Cell Line
;
Cloning, Molecular
;
Enzyme-Linked Immunosorbent Assay
;
Epitopes/biosynthesis/*immunology
;
Galactosyltransferases/biosynthesis/*genetics/*immunology
;
Gene Targeting
;
Gene Transfer Techniques
;
*Genetic Therapy
;
Genetic Vectors
;
Graft Rejection/*prevention & control
;
Graft vs Host Disease/prevention & control
;
Humans
;
Immune Tolerance
;
Mice
;
Mice, Knockout
;
Retroviridae/genetics
;
Swine
;
*Transplantation, Heterologous
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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