RECEPTORS IN PROXIMAL TUBULAR EPITHELIAL-CELLS FOR TUBULOINTERSTITIALNEPHRITIS ANTIGEN

Tubulointerstitial nephritis antigen (TIN-ag) is a novel basement memb rane macromolecule that is involved in human antitubular-basement-memb rane-mediated tubulointerstitial nephritis. The presence of antibodies to TIN-ag may result in an alteration of proximal tubule epithelial c ell interaction with surrounding matrix and contribute to the pathogen esis of immune-mediated tubulointerstitial disease. To study the adhes ive interactions between TIN-ag and proximal tubule epithelial cells a nd the macromolecules that mediate these interactions, an immortalized proximal tubular epithelial cell line from normal adult human kidney (HK-2) was used. Plastic-coated TIN-ag was able to promote adhesion of HK-2 cells in a concentration-dependent manner. The strength of the a dhesive interaction was comparable to that of type IV collagen or lami nin. To explore which members of the integrin family of cell surface r eceptors were involved in this interaction, we performed fluorescence activated cell sorting (FAGS) analysis and adhesion-inhibition studies using monoclonal antibodies against various integrins. Both approache s suggested that integrins alpha 3 beta 1 and alpha nu beta 3 are cruc ial for the adhesion of proximal tubule epithelial cells on TIN-ag, an d that they are probably using independent domains of TIN-ag for their action. These data will help us to understand the interactions betwee n proximal tubule epithelial cells and the underlying basement membran e, and will provide clues to the pathogenesis of kidney tubular diseas es at the molecular level.