Expression of lactoferrin in the kidney: Implications for innate immunity and iron metabolism

Background Sequestering of free iron by lactoferrin (LF) is important in th e defense against bacteria. In a screening for LF expression in various org ans, high levels of LF mRNA were detected in human kidney. This indicated t hat LF is produced by the kidney and that it may participate in innate immu nity of this organ. Methods and Results. Antibody staining and in situ hybridization of paraffi n-embedded kidney sections showed that LF is expressed in cells lining the distal collecting ducts of the medulla. High levels of both protein and mRN A were detected in these cells. However, a clear difference in the distribu tion of mRNA and protein within the tissue was observed. LF mRNA was detect ed along a relatively large portion of the tubuli, whereas LF antigen was f ound mainly in the very distal regions of the same tubuli. This indicates t hat LF is released by large regions of the tubuli and possibly reabsorbed i n the most distal parts. Using enzyme linked immunosorbent assay, only very low LF levels were detected in urine. Conclusion. The present study shows that LF is produced by the kidney and t hat both LF mRNA and protein are distributed in a highly ordered fashion. T his latter finding, together with the very low levels of LF detected in uri ne, indicates that LF may contribute to the immune defense in the kidney by reduction of available free iron in the urine. Other possibilities are tha t LF may play a role in the iron metabolism by recovering free iron from ur ine and making it available for metabolic use, and that LF may participate in the antioxidant defense systems protecting the kidney against nonmicrobi al oxidative injury, that is, ischemia, reperfusion and inflammation.