title: Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40.
abstract: BACKGROUND
  Platelets are potential contributors to glomerular injury via the release of chemotactic and/or mitogenic mediators upon activation or through direct CD154/CD40-dependent interaction with cell components of the glomerulus. We examined whether platelets could activate mesangial cells and the potential role of the platelet-associated CD154.
  
  
  METHODS
  Thrombin-activated platelets from systemic lupus erythematosus (SLE) patients or from disease or healthy controls were grown with human mesangial cells in the presence or not of a neutralizing anti-CD154 antibody either in contact or in a noncontact setting, the platelets and mesangial cells being separated by a pore size semipermeable membrane. The induction of mesangial cell surface antigens was assayed by flow cytometry. The quantification of mesangial cell proliferation was performed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the production of transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor (PDGF) and soluble CD40 were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Activated platelets from patients with SLE could induce an up-regulation of the expression of CD40 on mesangial cells with a concomitant release of soluble CD40. This induction required a direct contact between platelets and mesangial cells and was dependent upon the platelet-associated CD154. Pathologic consequences of the up-regulation of CD40 were a CD40-dependent stimulation of the proliferation of mesangial cells and a CD40-dependent increased production of TGF-beta1 by these cells.
  
  
  CONCLUSIONS
  Platelets from patients with SLE can activate mesangial cells through CD40/CD154 interactions, leading to an induction of proliferation of the mesangial cells and an enhanced production of TGF-beta1, a profibrotic cytokine.
authors.affiliation: Département de Néphrologie, Hôpital Pellegrin, Bordeaux, France. yahsou.delmas@chu-bordeaux.fr
authors.forename: Yahsou
authors.initials: Y
authors.lastname: Delmas
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Viallard
authors.forename: Anne
authors.initials: A
authors.lastname: Solanilla
authors.forename: Julien
authors.initials: J
authors.lastname: Villeneuve
authors.forename: Jean-Max
authors.initials: JM
authors.lastname: Pasquet
authors.forename: Francis
authors.initials: F
authors.lastname: Belloc
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dubus
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.forename: Patrick
authors.initials: P
authors.lastname: Blanco
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pellegrin
authors.forename: Alan T
authors.initials: AT
authors.lastname: Nurden
authors.forename: Christian
authors.initials: C
authors.lastname: Combe
authors.forename: Jean
authors.initials: J
authors.lastname: Ripoche
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D015539:Platelet Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000502:physiology
chemical_list: D019013:CD40 Antigens; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D023201:CD40 Ligand