title: Progressive reactive lymphoid connective tissue disease and development of autoantibodies in scavenger receptor A5-deficient mice.
abstract: Scavenger receptor A5 (SCARA5) is a member of the class A scavenger receptors, with most similarity to SCARA1 (SR-A) and SCARA2 (MARCO), which are primarily expressed by macrophages and dendritic cells, in which they participate in clearance of various polyanionic macromolecules, pollution particles, and pathogens. The biological role of SCARA5 has been unknown. Herein, we show that SCARA5 is an endocytotic receptor whose ligand repertoire includes the typical scavenger receptor ligands, whole bacteria, and purified Gram-negative bacterial lipopolysaccharide. In contrast to expression of SCARA1 and SCARA2 in immune cells, SCARA5 is found in a subset of fibroblast-like cells in the interstitial stroma of most organs, with additional expression in the epithelial cells of testis and choroid plexus. SCARA5-null mice develop with age lymphoid cell accumulation in many organs, in particular the lungs, and show decreased endocytotic function in fibroblasts. Furthermore, about one-third of the mice develop antinuclear antibodies. These disturbances are reminiscent of those found in many human autoimmune connective tissue disorders, which suggests that defects in fibroblast SCARA5 can underlie some forms of autoimmune disease.
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Juha Risto Matias
authors.initials: JR
authors.lastname: Ojala
authors.forename: Timo
authors.initials: T
authors.lastname: Pikkarainen
authors.forename: Göran
authors.initials: G
authors.lastname: Elmberger
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016466:CHO Cells; D002469:Cell Separation; D003240:Connective Tissue Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D006224:Cricetinae; D003412:Cricetulus; D018450:Disease Progression; D004705:Endocytosis; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D006801:Humans; D008221:Lymphoid Tissue / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C511405:SCARA5 protein, mouse; D051117:Scavenger Receptors, Class A