Urinary antigens as markers of papillary toxicity. II: Application of monoclonal antibodies for the determination of papillary antigens in rat urine

We have previously reported the preparation of monoclonal antibodies specif ic for antigens localized in the rat renal papilla. Three of the monoclonal antibodies reacting with antigens localized in papillary and cortical coll ecting duct epithelia were selected for the development of enzyme-linked im munosorbent assay (ELISA)-type assays. The papillary antigens ('PapA') dete rmined in these tests were designated PapA1 (applying the monoclonal antibo dy PapX 5C10), PapA2 (applying the monoclonal antibody PapX 12F6), and PapA 3 (applying the monoclonal antibody PapXI 3C7). Using these assays antigen excretion was determined in the urine of rats. Depending on the test compou nd used, the application route, and the dose, the observed antigen release patterns differed. Whereas after a single intraperitoneal application of 2- bromoethanamine or of propyleneimine an increased release of PapA1 but not of the two other antigens was observed oral application of bromoethanamine had minor effects. In contrast, both a single intraperitoneal application o r repeated oral applications of indomethacin resulted in an increased relea se of all the three antigens. Daily application of ipsapirone in the diet o r in drinking water resulted in significantly elevated urinary release of P apA1 which increased incrementally for the duration of the application. Rel ease of PapA2 and PapA3 was not affected and remained in the normal range. These results show that with the tests developed changes in the rat renal p apilla caused by xenobiotics can be detected early by urinary analysis and monitored during follow-up studies. Moreover, the different antigen release patterns obtained after application of the different compounds suggest a p ossible differing mode of action.