title: Ly-6 in kidney is widely expressed on tubular epithelium and vascular endothelium and is up-regulated by interferon gamma.
abstract: 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.
authors.affiliation: Division of Nephrology and Immunology, University of Alberta, Edmonton, Canada.
authors.forename: P G
authors.initials: PG
authors.lastname: Blake
authors.forename: J
authors.initials: J
authors.lastname: Madrenas
authors.forename: P F
authors.initials: PF
authors.lastname: Halloran
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism; D007684:Kidney Tubules / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009393:Nephritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins; D014018:Tissue Distribution; D015854:Up-Regulation
chemical_list: D000950:Antigens, Ly; D015342:DNA Probes; D008565:Membrane Proteins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D004247:DNA