title: Binding of the chemokine SLC/CCL21 to its receptor CCR7 increases adhesive properties of human mesangial cells.
abstract: BACKGROUND
  Adherence of human mesangial cells to the surrounding matrix contributes to glomerular homeostasis and is important for the maintenance of glomerular architecture and function in normal adult human kidney. The expression of chemokines and corresponding chemokine receptors on adjacent intrinsic renal cells indicates a novel chemokine/chemokine receptor function on nonimmune cells important for glomerular homeostasis. A constitutive expression of the chemokine SLC/CCL21 on human podocytes and of its corresponding receptor CCR7 on mesangial cells was shown before. SLC/CCL21 has a positive effect on proliferation and migration of mesangial cells and leads to increased cell survival in Fas-induced apoptosis. In leukocytes chemokines mediate integrin-dependent firm adhesion. Therefore, we examined the influence of chemokine receptor CCR7 activation by SLC/CCL21 on adhesive properties of human mesangial cells to matrix molecules.
  
  
  METHODS
  Adhesion assays, mechanical detachment assays, and evaluation of integrin activation by integrin-linked kinase activity were performed. Changes in the cytoskeletal F-actin were illustrated by phalloidin immunofluorescence staining.
  
  
  RESULTS
  SLC/CCL21 stimulation enhanced adhesiveness to fibronectin in a time- and concentration-dependent manner. SLC/CCL21 also increased the firmness of mesangial cells adhesion as judged by detachment assays. Furthermore activation of integrin-linked kinase occurred with SLC/CCL21 addition to mesangial cells, resulting in increased phosphorylation of glycogen synthase kinase-3 (GSK-3) and protein kinase B (PKB/Akt). Exposure of mesangial cells to SLC/CCL21 also resulted in F-actin rearrangements with membrane ruffling and extensions leading to bridging between mesangial cells.
  
  
  CONCLUSIONS
  Activation of CCR7 on mesangial cells by SLC/CCL21 enhances the degree and firmness of cell adhesion and increases cell spreading and the formation of cell-cell contacts. This includes integrin-linked kinase activation and F-actin rearrangements. Thus, local chemokine generation and chemokine receptor expression on mesangial cells may play an important role in the maintenance of glomerular homeostasis and in local remodeling processes.
authors.affiliation: Nephrologisches Zentrum, Medizinische Poliklinik, Ludwig-Maximilians-Universität München, Germany. bernhard.banas@klinik.uni-regensburg.de
authors.forename: Bernhard
authors.initials: B
authors.lastname: Banas
authors.forename: Markus
authors.initials: M
authors.lastname: Wörnle
authors.forename: Monika
authors.initials: M
authors.lastname: Merkle
authors.forename: Mercedes
authors.initials: M
authors.lastname: Gonzalez-Rubio
authors.forename: Holger
authors.initials: H
authors.lastname: Schmid
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Pietrzyk
authors.forename: Monika
authors.initials: M
authors.lastname: Fink
authors.forename: Guillermo
authors.initials: G
authors.lastname: Perez de Lema
authors.forename: Detlef
authors.initials: D
authors.lastname: Schlöndorff
mesh_terms: D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002461:Cell Line, Transformed; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*
chemical_list: D000199:Actins; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D019742:Chemokines, CC; D005353:Fibronectins; D016023:Integrins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine