title: Selective binding and presentation of CCL5 by discrete tissue microenvironments during renal inflammation.
abstract: T cells are differentially recruited to the tubulointerstitium during renal inflammation. The selective presentation of chemokines by surface structures may in part underlie this phenomenon. In an attempt to better characterize the presentation of chemokines by tissue environments an exemplary chemokine with a well-defined structure was selected, and a binding assay for the protein on fixed archival tissue sections was developed. This article describes the selective binding of the chemokine CCL5 to renal structures. CCL5 was shown to bind to endothelial regions, interstitial extracellular matrix, tubular epithelial cells, and tubular basement membranes but rarely to glomerular structures in well-preserved kidneys. In contrast, binding of CCL5 to glomerular components was seen in renal biopsies with acute allograft glomerulitis (in which T cells accumulate in glomeruli). The N terminus mediates receptor binding, whereas two clusters of basic amino acid residues ((44)RKNR(47) and (55)KKWVR(59)) are involved in the presentation of CCL5 by extracellular structures. Mutation of either loop abrogated CCL5 binding to tissue sections. Variations of the N terminus and a mutation that prevents higher order oligomerization did not change the binding pattern. The data suggest that renal compartments differ in their capacity to present chemokines, which may help explain the differential recruitment of leukocytes during allograft injury. Both clusters of basic residues in CCL5 are necessary for sufficient binding of CCL5 to tissue sections.
authors.affiliation: Medizinische Poliklinik-Innenstadt, University of Munich, Pettenkoferstrasse 8a, 80336 Munich, Germany. stephan.segerer@lrz.uni-muenchen.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.forename: Roghieh
authors.initials: R
authors.lastname: Djafarzadeh
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.forename: Christian
authors.initials: C
authors.lastname: Weingart
authors.forename: Dontscho
authors.initials: D
authors.lastname: Kerjaschki
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Kungl
authors.forename: Heinz
authors.initials: H
authors.lastname: Regele
authors.forename: Amanda E I
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D001706:Biopsy; D018946:Chemokine CCL5 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation; D008969:Molecular Sequence Data; D009392:Nephrectomy; D009393:Nephritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5