Neutrophil Gelatinase-associated Lipocalin, a Siderophore-binding Eukaryotic Protein

The Granulocyte Research Laboratory, Department of Hematology, University of Copenhagen, Rigshospitalet-4042, 9 Blegdamsvej, Copenhagen Ø, DK 2200, Denmark.
BioMetals (Impact Factor: 2.5). 05/2006; 19(2):211-5. DOI: 10.1007/s10534-005-3251-7
Source: PubMed


NGAL (neutrophil gelatinase-associated lipocalin) also known as lcn2 or siderochalin is constitutively expressed in myelocytes and stored in specific granules of neutrophils. It is highly induced in a variety of epithelial cells during inflammation. Analysis of the crystal structure of NGAL expressed in E.coli showed that NGAL has the ability to bind catecholate type siderophores and in this way prevent bacteria from acquisition of siderophore-bound iron. NGAL (or 24p3 as the highly homologous murine orthologue is named) knock out mice have a profound defect in defense against E.coli after intraperitoneal injection. This defect can be mimicked in wild-type mice by providing siderophore iron, which cannot be sequestered by NGAL, testifying to the specific role of NGAL as a siderophore binding protein in innate immunity. Megalin, a scavenger receptor functions as a receptor for NGAL and mediates uptake into endosomes, but other NGAL receptors are likely to exist.

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    • "Lipocalin 2 (LCN2), also known as siderocalin, 24p3, uterocalin, and neutrophil gelatinase-associated lipocalin (NGAL), is a recently identified glycoprotein stored in neutrophil granules [120] but mainly produced by WAT [121, 122]. LCN2 has been isolated in different isoforms and its functions are carried out by the activation of the cellular receptor megalin [123]. "
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    • "In addition, fetal sCysC levels do not show any relationship to maternal sCysC levels [10]. NGAL, known as Lipocain-2(lcn2) as well as Siderocalin, is an ubiquitos 25 kDa protein of 178 amino acids, covalently bound to gelatinize from human neutrophils [11]. One in particular, NGAL was recently identified as one of the earliest and most robustly induced proteins by the kidney after ischemic injury. "
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    • "Siderocalin, which is also known as lipocalin-2 or neutrophil-gelatinase-associated lipocalin (Ngal), is produced by neutrophil granules and in epithelial cells in response to the proinflammatory cytokine IL-1β [21]. Numerous pathogenic microorganisms secrete small organic siderophores to scavenge for iron. "
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