THE ROLE OF INTEGRINS IN IGA NEPHROPATHY

The complicated network of immune reactions leading to mesangial cell activation and glomerular sclerosis in IgA nephropathy (IgAN) involves interactions between infiltrating cells, mesangial cells and mesangia l matrix which are mediated by adhesion molecules. Integrin expression on mesangial cells in culture has recently been described. In the pre sent work we investigated whether integrin expression on cultured huma n mesangial cells (MC) and mesangial matrix production could be modula ted by mesangial matrix components, or by other proteins which may com e into contact with MC during pathologic conditions, such as fibrinoge n and von Willebrand factor. Moreover, we evaluated the effects induce d by polymeric IgA or aggregated IgA or mixed IgA/IgG aggregates on in tegrin expression. To elucidate a possible role for abnormally glycosy lated IgA, we tested IgA. pretreated with various enzymes specific for carbohydrate residue components of the side carbohydrate chains of Ig A molecules. We found that cultured mesangial cells, highly express th e av beta 3 integrin receptor for vitronectin and to a lesser extent t he alpha 3 beta 1 receptor for fibronectin and collagens. Among these integrins, alpha v beta 3 is modulated by matrix components and partic ularly enhanced when cells are incubated with proteins which can be ab normally present in the mesangial area, such as fibrinogen, collagen I and von Willebrand factor. IgA and aggregated IgA can modify integrin expression, inducing a decrease in alpha 3 beta 1 and an increase in alpha v expression. Moreover, sugars can affect these interactions, si nce desialylated IgA enhance the expression of integrin beta 3 chain o n cultured mesangial cells and sialic acid per se strongly inhibits it . Conversely, other sugars, represented in the carbohydrate chains of IgA(1) including mannose and N-acetylgalactosamine, were found to enha nce alpha v expression. Our data suggest that the interactions of nati ve polymeric IgA, IgA or IgA/IgG aggregates, as well as IgA with alter ed glycosylation may result in structural rearrangement of mesangial i ntegrins, possibly reflecting on mesangial matrix composition.