Microparticles may contribute to the pathogenesis of systemic lupus erythematosus

Autor: G. Nagy, M. Pasztoi, M. Trenkmann, A. Haris, K. Polner, F. Moritz, J.H.W. Distler, T. Hauser, M. Brock, S. Ulrich, R.E. Gay, A. Falus, B.A. Michel, R. Speich, O. Distler, D.S. Pisetsky, E. Buzas, S. Gay, L.C. Huber
Rok vydání: 2008
Předmět:
Zdroj: Joint Bone Spine. 75:248
ISSN: 1297-319X
DOI: 10.1016/j.jbspin.2008.01.017
Popis: Objective Microparticles are a heterogeneous population of small, membrane-coated vesicles that represent subcellular elements for cell signaling and intercellular communication in inflammation. Microparticles can be released by virtually all cell types upon activation or apoptosis. These particles have diverse biological properties and have been implicated as disease mediators that can induce inflammation as well as modulate apoptosis of target cells. Since the pathogenesis of systemic lupus erythematosus may involve aberrant apoptosis and clearance of dying cells, microparticles could contribute to disease manifestations of this prototypic autoimmune disease. Methods Quantification and characterization of microparticles were performad by flow cytometry. T cells were isolated by positive selection magnetic cell sorting. For release of microparticles, human U937 cells were stimulated with staurosporine then cell culture supernatants were centrifuged. Isolated microparticles were then quantified and added to cultured T cells. After 48 hours, rates of apoptosis and cell growth were measured by flow cytometry using Annexin V and the MTS proliferation assay. Results Our data indicate that the levels of microparticles derived from B-lymphocytes and monocytes, but not from T cells, are elevated in the blood of SLE patients compared to healthy controls. Furthermore, in experiments in which microparticles from U937 cells were added to isolated T cells in vitro, proliferation was induced dose-dependently in T cells from SLE patients and healthy controls. In contrast, the apoptosis rate was unaffected in normal T cells, whereas the data on the apoptosis rate of lupus T cells showed strong reactions upon the addition of microparticles, suggesting a differential sensitivity of SLE T cells to signalling by these structures. Conclusion Together, these findings emphasize the potential role of microparticles as mediators of autoimmunity.
Databáze: OpenAIRE