Immunological comparison of renin substrate with erythropoietin

Immunological similarities between human renin substrate and erythropoietin were studied. Purified renin substrate was coupled to erythrocytes, and haemagglutination was demonstrated both with antisera against renin substrate and erythropoietin. Extensive purification of renin substrate was performed on fast protein liquid chromatography (FPLC), and fractions were collected and assayed for renin substrate and erythropoietin. Following FPLC, the major protein peak corresponded to renin substrate, whereas erythropoietin immunoactivity dissociated from this peak. Iodinated renin substrate and erythropoietin-containing fractions showed specific binding to both renin substrate and erythropoietin antisera. The results suggest that human erythropoietin or erythropoietin-like material may co-purify with renin substrate, and that preparative procedures like FPLC should be included to obtain pure angiotensinogen preparations. While renin substrate and erythropoietin, judging from the present results and cloned DNA sequences, appear completely unrelated, the possible relationship between renin substrate and other erythropoietic factors remains unsettled.