Cu(II) and Zn(II) complexes with hyaluronic acid and its sulphated derivative. Effect on the motility of vascular endothelial cells.

With the aim of improving the compatibility of biomaterials to be used for the construction of cardiovascular prosthesis, we have designed bioactive macromolecules resulting from chemical modifications of hyaluronic acid (Hyal). The stability constants of Cu(II) and Zn(II) complexes with the sulphated derivative of hyaluronic acid (HyalS3.5) were evaluated. Two different complexes have been found for each metal ion, CuL, Cu(OH)2L and ZnL, Zn(OH)2L (L means the disaccharide unit of the ligands) in aqueous solution at 37 degrees C. The dihydroxo Cu(II) complex was present in high percentage at pH=7.4. On the contrary, the Zn(II) ion was present with a relatively low percentage of both complexes. The ability to stimulate endothelial cell adhesion and migration was evaluated for Hyal, HyalS3.5 and their complexes with Cu(II) and Zn(II) ions. The results revealed that Hyal and [Cu(OH)2HyalS3.5](4.5)- induced cell adhesion, while [ZnHyalS3.5](2.5)- and [Zn(OH)2HyalS3.5](4.5)- inhibited the process. The chemotactic activity of increasing concentrations of the above complexes was also evaluated, demonstrating that [Cu(OH)2HyalS3.5](4.5)- complex at 1 microM concentration was the most active in inducing cell migration. These results have been also strengthened by analysing adherent cell migration in agarose. In conclusion, sulphated hyaluronic acid coordinated to Cu(II) seems to be a promising matrix molecule for the construction of cardiovascular prosthesis.

Phagocytosis of Plasmodium falciparum-infected human red blood cells by human monocytes: involvement of immune and nonimmune determinants and dependence on parasite developmental stage.

The stage-dependent phagocytosis of Plasmodium falciparum-infected erythrocytes (IRBC) opsonized with nonimmune serum has been investigated. An average of 2.9 red blood cell (RBC) harboring ring-forms (RIRBC) and 7.5 RBC infected with trophozoites (TIRBC) or schizonts (SIRBC) were ingested per monocyte, in comparison with 0.8 noninfected RBC (NRBC) or 5 RBC oxidatively damaged with diamide. Abrogation of generation of complement component C3b or blockage of its binding to the phagocyte inhibited phagocytosis of RIRBC by 78% to 95% and of TIRBC by 25% to 50%. Blockage of immunoglobulin G (IgG) binding reduced phagocytosis of both RIRBC and TIRBC nonsignificantly by 14%. Preincubation of monocytes with phosphatidylserine (PS)-containing liposomes reduced phagocytosis of TIRBC by 22%, but had little effect on RIRBC. Residual, noncomplement, non-IgG-, and non-PS-dependent phagocytosis amounted to 6% to 18% of total phagocytosis in RIRBC and TIRBC, respectively. RIRBC bound 2.5 times more protein A and 3.1 times more anti-C3c (a stable derivative of C3b) antibodies, and TIRBC bound 20 times more protein A and 6.8 times more anti-C3c antibodies than NRBC. Phagocytosis of oxidatively damaged RBC and RIRBC are similar, whereas a higher portion of phagocytosis appears to be noncomplement-dependent and PS-suppressible in TIRBC. It is concluded that RIRBC generate recognition signals similar to those present in oxidatively damaged or senescent RBC. Extensive membrane modifications in TIRBC produce additional, hitherto undefined signals that induce much higher and qualitatively distinct phagocytosis.