Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40

• Published in: Kidney international Vol. 68; no. 5; pp. 2068 - 2078
• Main Authors: Delmas, Yahsou, Viallard, Jean-François, Solanilla, Anne, Villeneuve, Julien, Pasquet, Jean-Max, Belloc, Francis, Dubus, Isabelle, Dachanet-Merville, Julie, Merville, Pierre, Blanco, Patrick, Pellegrin, Jean-Luc, Nurden, Alan T., Combe, Christian, Ripoche, Jean
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2005; Nature Publishing; Elsevier Limited
• Subjects: Adult; Aged; Biological and medical sciences; blood platelets; Blood Platelets - cytology; Blood Platelets - metabolism; CD40 Antigens - metabolism; CD40 ligand; CD40 Ligand - metabolism; Cell Communication - physiology; Cells, Cultured; Coculture Techniques; Female; glomerular mesangium; Humans; lupus erythematosus; Lupus Erythematosus, Systemic - metabolism; Lupus Erythematosus, Systemic - pathology; Male; Medical sciences; Mesangial Cells - cytology; Mesangial Cells - metabolism; Middle Aged; Nephrology. Urinary tract diseases; Platelet Activation; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; systemic; transforming growth factor beta; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta1; Up-Regulation - physiology; systemic; blood platelets; glomerular mesangium; lupus erythematosus; transforming growth factor beta; CD40 ligand; Connective tissue disease; Skin disease; Nephrology; Platelet activation; Mesangial cell; Induction; Transforming growth factor; Autoimmune disease; Systemic; Kidney; Blood; Urology; Renal glomerulus; Platelet; Systemic lupus erythematosus; Urinary system; Systemic disease; Lupus erythematosus; Disseminated
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1111/j.1523-1755.2005.00663.x

Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40. 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. 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-β1 (TGF-β1), platelet-derived growth factor (PDGF) and soluble CD40 were measured by enzyme-linked immunosorbent assay (ELISA). 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-β1 by these cells. 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-β1, a profibrotic cytokine.