The interactions between charged unilamellar vesicles of different size prepared from mixtures of egg lecithin (EPC), cholesterol, and a charged component, either stearylamine or dicetyl phosphate, were investigated. Several techniques, i.e. fluorescence spectroscopy, 133Cs-NMR, light scattering measurements, and electron and optical microscopies in dilute aqueous solutions, provided evidence that vesicles bearing opposite charges interact via contact followed by lipid exchange; the progressive charge neutralization is shown by 133Cs-NMR to occur without fusion of vesicle internal pools. Vesicle size determines as diverse features as contact duration, extent of lipid exchange, and final distribution of surface charge among the vesicle mixture.

Glomerulonephritis is characterized by the proliferation and apoptosis of mesangial cells (MC). The parathyroid-hormone related protein (PTHrP) is a locally active cytokine that affects these phenomena in many cell types, through either paracrine or intracrine pathways. The aim of this study was to evaluate the effect of both PTHrP pathways on MC proliferation and apoptosis. In vitro studies were based on MC from male transgenic mice allowing PTHrP-gene excision by a CreLoxP system. MC were also transfected with different PTHrP constructs: wild type PTHrP, PTHrP devoid of its signal peptide, or of its nuclear localization sequence. The results showed that PTHrP deletion in MC reduced their proliferation even in the presence of serum and increased their apoptosis when serum-deprived. PTH1R activation by PTHrP(1-36) or PTH(1-34) had no effect on proliferation but improved MC survival. Transfection of MC with PTHrP devoid of its signal peptide significantly increased their proliferation and minimally reduced their apoptosis. Overexpression of PTHrP devoid of its nuclear localization sequence protected cells from apoptosis without changing their proliferation. Wild type PTHrP transfection conferred both mitogenic and survival effects, which seem independent of midregion and C-terminal PTHrP fragments. PTHrP-induced MC proliferation was associated with p27(Kip1) down-regulation and c-Myc/E2F1 up-regulation. PTHrP increased MC survival through the activation of cAMP/protein kinase A and PI3-K/Akt pathways. These results reveal that PTHrP is a cytokine of multiple roles in MC, acting as a mitogenic factor only through an intracrine pathway, and reducing apoptosis mainly through the paracrine pathway. Thus, PTHrP appears as a probable actor in MC injuries.