Renal interstitial cell infiltration in rats induced by immune reactions around proximal tubular basement membrane

Abstract

Background. Since it has been shown that the severity of tubulointerstitial nephritis (TIN) and, in particular, the degree of monocyte infiltration, correlate both with the degree of renal impairment at biopsy and with the risk of disease progression, attention has been focused on the development of experimental models of TIN.

Methods. We induced TIN by injecting rats with a monoclonal antibody, R3b1 (which binds around the proximal tubular basement membrane (TBM) but not to glomeruli), and also by enhancing the host immune reactions to R3b1 bound around the TBM.

Results. R3b1 was demonstrated to bind around the proximal TBM but not to glomeruli in vitro and also in vivo. The binding of R3b1 around the proximal TBM induced mild focal ED-1-positive cell infiltration in the interstitium. Enhanced host immune reaction to bound R3b1 resulted in a transient increase in the number of focally infiltrated ED-1-positive cells in the interstitium, although it shortened the period during which R3b1 was demonstrable around the TBM. There were no significant increases in immunostaining for vimentin and osteopontin, or collagen types I and IV, suggesting that, immunohistochemically, there was no tubular cell damage and no interstitial fibrosis, respectively. Light microscopy revealed focal interstitial cell infiltration, supporting the results obtained by immunofluorescence as ED-1-positive cell infiltration. Tubular cell atrophy, enlargement, and interstitial fibrosis were not observed.

Conclusions. The enhancement of host immune reaction to mouse immunoglobulins, i.e., to monoclonal antibody R3b1 bound around the proximal TBM induced by two immunizations, resulted in an increased degree of focal ED-1-positive cell infiltration in the interstitium, but no demonstrable tubular cell injury or interstitial fibrosis. R3b1 did not induce progressive tubulointerstitial injury, even in rats preimmunized and booster-immunized with mouse IgG.