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Delmas, Y. et al.

Delmas, Viallard, Solanilla, Villeneuve, Pasquet, Belloc, Dubus, Déchanet-Merville, Merville, Blanco, Pellegrin, Nurden, Combe, Ripoche,

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. CONCLUSION: 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.[1]

References

Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40. Delmas, Y., Viallard, J.F., Solanilla, A., Villeneuve, J., Pasquet, J.M., Belloc, F., Dubus, I., Déchanet-Merville, J., Merville, P., Blanco, P., Pellegrin, J.L., Nurden, A.T., Combe, C., Ripoche, J. Kidney Int. (2005) [Pubmed]

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