Ly-6 in Kidney Is Widely Expressed on Tubular Epithelium and Vascular Endothelium and Is Up-regulated by Interferon Gamma
Journal of the American Society of Nephrology
Ly-6 is a multigene family of murine polymorphic cell membrane proteins that are glycosydlphosphatidylinositol anchored, widely expressed on lymphoid tissue, and homologous to the recently described human CD59. An unexpected feature of Ly-6 is its high level of expression in the kidney. This renal expression and its interferon (IFN)-gamma inducibility in murine strains expressing different Ly-6 haplotypes were studied with monoclonal antibodies and cDNA probes that recognize Ly-6A/E and Ly-6C. Ly-6 expression was much more extensive in the kidney than in other parenchymal organs. Ly-6A.1/E.2 was extensively expressed on vascular endothelium and on tubular epithelium, particularly in the distal nephron. Pattern of expression differed between strains expressing A and E alleles. Ly-6C was not detected by monoclonal antibodies but was detected by oligonucleotide-specific probes. Treatment with recombinant IFN-gamma or IFN-inducing agents increased Ly-6 expression markedly, particularly on the luminal aspect of the proximal tubular epithelium, where Ly-6A/E became prominent. This luminal expression is typical for glycosydlphosphatidylinositol-anchored proteins but contrasts with that of other molecules, such as major histocompatibility classes I and II, which are generally expressed on the basolateral surface of the tubular epithelium. Up-regulation occurred within 6 h of IFN-gamma treatment and returned to normal by 48 h. Similar up-regulation of Ly-6 was seen in murine lupus nephritis and in mercuric chloride nephropathy. The characteristics of renal Ly-6, such as its IFN-gamma responsiveness, endothelial and tubular expression, polymorphism, strong antigenicity, and possible allelic regulation, make it a candidate to be a target molecule in alloresponses. The renal expression of Ly-6 is similar to that of CD59 in the human kidney, supporting the suggestion that these proteins are closely related.