Expression and function of fibronectin receptors on peripheral mononuclear cells in IgA nephropathy

The ß1 integrin family, major adhesive receptors forthe extracellular matrix (ECM), have been reported to be presentin normal and diseased kidneys. Attachment of glomerular cellsto ECM is mediated by ß1 integrins. Several membersof the ß1 integrins are referred to as VLA (very lateactivation) antigens. Peripheral mononuclear cells also expressVLA antigens in both resting and activated states. We examinedthe expression and function of VLA antigens on peripheral lymphocytesand monocytes in patients with IgA nephropathy using monoclonalantibodies (mAbs) specific for VLA -chains. Peripheral lymphocytesfrom patients with IgA nephropathy expressed VLA-4 and 5, butnot VLA-1 2 or 3. Peripheral monocytes from patients with IgAnephropathy expressed VLA-2 4 and 5, but not VLA-1 or 3. Theexpression of VLA adhesive receptors was observed in healthyindividuals. Adhesion assay to fibronectin revealed augmentedadhesion of mononuclear cells in IgA nephropathy (P<0.05),and this increased adhesion was inhibited by mAbs to VLA-4 and5. The expression of ß1 integrins in IgA nephropathywas similar to that of healthy individuals, but the functionof these molecules in terms of adhesion to fibronectin thoughVLA-4 and VLA-5 is increased in these patients. These findingssuggest that the activation of fibronectin receptors on peripheralmononuclear cells plays an important role in the pathogenicprocess of IgA nephropathy.