Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40.
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.
Delmas
Yahsou
Y
Département de Néphrologie, Hôpital Pellegrin, Bordeaux, France. yahsou.delmas@chu-bordeaux.fr
Viallard
Jean-François
JF
Solanilla
Anne
A
Villeneuve
Julien
J
Pasquet
Jean-Max
JM
Belloc
Francis
F
Dubus
Isabelle
I
Déchanet-Merville
Julie
J
Merville
Pierre
P
Blanco
Patrick
P
Pellegrin
Jean-Luc
JL
Nurden
Alan T
AT
Combe
Christian
C
Ripoche
Jean
J
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
D019013:CD40 Antigens; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D023201:CD40 Ligand