NEPHRITOGENICITY AND ALPHA-CHAIN COMPOSITION OF NC1 FRACTIONS OF TYPE-IV COLLAGEN FROM BOVINE RENAL BASEMENT-MEMBRANE

Nephritogenicity (anti-GBM-nephritis-inducing activity) and alpha-chai n composition of globular-domain (NC1) fractions of type IV collagen f rom bovine renal, pulmonary, and placental basement membranes (BMs) wa s examined by injecting these fractions with adjuvant into WKY/NCrj ra ts and by Western blotting using epitope-defined monoclonal antibodies to the six different a chains of type IV collagen. A purified nephrit ogenic fraction from renal BM contained alpha 1-alpha 6(IV)NC1, wherea s a non-nephritogenic fraction contained only alpha 1-alpha 2(IV)NC1. Renal and pulmonary NC1 had strong nephritogenic activity; placental N C1 had weak activity. The renal and pulmonary fractions contained alph a 1-alpha 6(IV)NC1, and the placental fraction had a large amount of a lpha 1-alpha 2(IV)NC1 and a very small amount of alpha 3-alpha 6(IV)NC 1. Immunohistochemical study of bovine renal EM with the monoclonal an tibodies revealed that bovine glomerular BM contained alpha 1-alpha 5( IV) chains, but not the alpha 6(IV) chain. The absence of alpha 6(IV) chain in glomerular BM in bovine and in humans indicates that alpha 6( IV) chain is not a target antigen of anti-GBM nephritis. Nephritogenic ity is apparently a property of alpha 3-alpha 5(IV)NC1.