Heterogeneous expression of Gal alpha1-3Gal xenoantigen in pig kidney: a lectin and immunogold electron microscopic study
Strokan, V.; Mölne, J.; Svalander, C.T.; Breimer, M.E.
Transplantation 66(11): 1495-1503
1998
ISSN/ISBN: 0041-1337 PMID: 9869091 Document Number: 488893
Background. The Galalpha1-3Gal antigen (Galalpha) is the primary target for human natural anti-pig xenoantibodies. The presence of Galalpha has been shown in porcine endothelial cells (ECs) using light microscopy, whereas the expression of Galalpha in other cell structures in the porcine kidney is only partially characterized. Methods. Immunogold electron microscopy of pig kidney cryosections was performed using Griffonia simplicifolia isolectin B4 and affinity isolated human anti-Galalpha1-3Gal antibodies. Results. The most intense expression of Galalpha was found on the apical and basolateral portions of the plasma membrane of the proximal convoluted tubule segments 1 and 2 cells, whereas segment 3 and 4 cells were negative. A strong staining was found in peritubular capillary ECs and in the inner medullary and papillary collecting duct cells. Moderate labeling of ECs and subendothelium was observed in large blood vessels, whereas glomerular ECs reacted weakly. Additionally, glomerular parietal epithelial cells, connecting tubule cells, and some cortical collecting duct cells were labeled. Among interstitial cells, a part of type-1 cells and all type-2 cells were labeled, whereas others were negative. Conclusions. By immune electron microscopy, a detailed information of the Galalpha antigen distribution in porcine nephrons and blood vessels has been revealed, which clarifies conflicting data obtained by light microscopy. In addition, expression of the Galalpha antigen in the renal interstitial cells was documented for the first time. These data are of importance for the understanding of xenoantibody-mediated hyperacute rejection, for interpretation of pig kidney xenograft biopsies, and for generating transgenic pigs lacking the Galalpha epitope.