Neutrophil gelatinase-associated lipocalin (NGAL): a new piece of the anemia puzzle?

Neutrophil Gelatinase-Associated Lipocalin (NGAL), a small 25-kD peptide, originally discovered as an antibacterial factor of natural immunity and an acute-phase protein, represents a key factor in the regulation of erythrocyte growth due to its ability to inhibit the maturation and differentiation of bone marrow erythroid precursors. When a condition of primary anemia occurs, the body has a double response with respect to NGAL production and its systemic effects. Because NGAL is a protective, anti-oxidant factor, there is an increase in the peripheral production of the protein in order to counteract hypoxic stress. However, the increased systemic NGAL levels would have a negative impact on the bone marrow red cell homeostasis, thus the bone marrow counteracts this potential negative effect by reducing the production of NGAL by the same erythroid precursor and by enhancing the survival mechanisms of these cells. Several systemic diseases associated with the presence of secondary anemia, such as chronic renal failure, chronic inflammation and cancer, are known to induce a dramatic increase in circulating NGAL levels. This may represent a further, important cause of the development and worsening of anemia itself. From this point of view, NGAL may thus become an alternative therapeutic target for improving the treatment of secondary anemia related to these conditions.