Surface-adsorbed alpha1-microglobulin modulation of human fibroblasts spreading and matrix metalloproteinases release.

Abstract

The lipocalin alpha1-microglobulin (alpha1-m), an immunoregulatory protein produced by human hepatocytes and distributed in various organs and fluids, is physiologically adsorbed onto polymer surfaces from both serum and urine, and its adsorption correlated to the degree of surface hydrophobicity. Starting from the hypothesis that alpha1-m holds a modulatory role at the biomaterials-tissue interface, we have observed a dose-dependent reduction in adhesion of human fibroblasts (cell line MRC-5) seeded onto polystyrene (PS) in a serum-free medium in the presence of adsorbed alpha(1)-m (2.1+/-0.2 x 10(4) cells/cm2 at 200 ng/ml alpha1-m ) compared to cells seeded onto cell grade PS (2.9+/-0.05 x 10(4) cells/cm2) after 72 h. Moreover, in the presence of alpha1-m, adherent MRC-5 cells exhibit an altered shape due to inhibition of cell spreading, and release of matrix metalloproteinase -2 (gelatinase A, MMP-2) by fibroblasts was also increased by 1.6-1.9-fold after 72 h of incubation. These data extend the known spectrum of alpha1-m activities, suggesting a possible role of this protein in the complex series of events occurring at the tissue-biomaterial interface.