Dual Action of Neutrophil Gelatinase–Associated Lipocalin : Journal of the American Society of Nephrology (original) (raw)

Frontiers in Nephrology

Schmidt-Ott, Kai M.*; Mori, Kiyoshi†; Li, Jau Yi*; Kalandadze, Avtandil*; Cohen, David J.*; Devarajan, Prasad‡; Barasch, Jonathan*

*Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; †Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan; and ‡Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio

Address correspondence to: Dr. Jonathan Barasch, Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032. Phone: 212-305-1890; Fax: 212-305-3475; E-mail: [email protected]

Abstract

Neutrophil gelatinase–associated lipocalin (NGAL) is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL exerts bacteriostatic effects, which are explained by its ability to capture and deplete siderophores, small iron-binding molecules that are synthesized by certain bacteria as a means of iron acquisition. Consistently, NGAL deficiency in genetically modified mice leads to an increased growth of bacteria. However, growing evidence suggests effects of the protein beyond fighting microorganisms. NGAL acts as a growth and differentiation factor in multiple cell types, including developing and mature renal epithelia, and some of this activity is enhanced in the presence of siderophore:iron complexes. This has led to the hypothesis that eukaryotes might synthesize siderophore-like molecules that bind NGAL. Accordingly, NGAL-mediated iron shuttling between the extracellular and intracellular spaces may explain some of the biologic activities of the protein. Interest in NGAL has been sparked by the observation that NGAL is massively upregulated after renal tubular injury and may participate in limiting kidney damage. This review summarizes the current knowledge about the dual effects of NGAL as a siderophore:iron-binding protein and as a growth factor and examines the role of these effects in renal injury.