title: A novel splice variant of human L-selectin encodes a soluble molecule that is elevated in serum of patients with rheumatic diseases.
abstract: L-selectin, a type I membrane protein, is a leukocyte adhesion molecule that mediates both lymphocyte homing to peripheral lymph nodes and leukocyte accumulation at sites of inflammation. L-selectin is rapidly shed from the cell surface after cellular activation, and the ectodomain thus released is thought to account for high levels of soluble L-selectin in serum. In this study, we report the identification of a novel, naturally occurring isoform of the human L-selectin gene. Sequence analysis revealed that this isoform is generated by an alternative splicing event: the 7th exon of the human L-selectin gene, which encodes the region containing the transmembrane domain, is excluded, predicting a soluble protein product. The mRNA for this splice variant was expressed in lymphoid organs, where conventional L-selectin mRNA was also expressed. Activating T cells increased the variant mRNA and its ratio to the membrane form. Soluble L-selectin translated from the variant mRNA was present in human serum, albeit at a much lower level than that arising from ectodomain shedding, and was markedly elevated in patients with various rheumatic diseases, including rheumatoid arthritis and systemic lupus erythematosus. These observations indicate that some of the soluble L-selectin present in human serum arises through alternative splicing, which may be upregulated during lymphocyte activation in patients with various clinical conditions.
authors.affiliation: Department of Fundamental Biosciences, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan. Electronic address: tahirata@belle.shiga-med.ac.jp.
authors.forename: Takako
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Usui
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
authors.forename: Shio
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D002478:Cells, Cultured; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019041:L-Selectin / Q000097:blood / Q000235:genetics*; D012326:RNA Splicing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012216:Rheumatic Diseases / Q000097:blood*
chemical_list: D017931:DNA Primers; D019041:L-Selectin
keywords: Adhesion molecules; Alternative splicing; L-selectin; Leukocytes; Rheumatoid arthritis