Neutrophil Gelatinase Associated Lipocalin (NGAL), also known as Lipocalin-2 (LCN2), is a protein that plays a crucial role in the body’s innate immune response. It was first identified in a simian virus 40-infected murine kidney cell culture and later found to be associated with matrix metalloproteinase (MMP)-9, a gelatinase secreted by neutrophils for extracellular matrix remodeling . NGAL is involved in iron homeostasis, infection, and inflammation, making it a significant protein in various physiological and pathological processes .
NGAL is primarily known for its ability to bind and sequester iron, which is essential for bacterial growth. By binding to bacterial siderophores, NGAL limits the availability of iron to bacteria, thereby inhibiting their growth . This function is crucial in the body’s defense against bacterial infections. Additionally, NGAL binds to the mammalian siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA), ensuring that excess free iron does not accumulate in the cytoplasm, which could lead to high levels of reactive oxygen species .
NGAL is used as a biomarker for kidney injury due to its protease resistance and low molecular weight, which allows it to be excreted and detected in urine . Injured epithelial cells in the kidney secrete a monomeric form of NGAL, while activated neutrophils secrete a dimeric form. This distinction can potentially improve acute kidney injury (AKI) diagnostics by differentiating between NGAL of inflammatory origin and that of renal origin . Elevated NGAL levels are observed in both blood and urine within two hours of kidney injury, making it a more precise and sensitive marker for diagnosing AKI compared to serum creatinine levels .
NGAL has also been recognized for its roles in gut-origin sepsis. It mitigates gut barrier injury by maintaining microbiota homeostasis, exerting antioxidant effects, deactivating macrophages, and inducing immune cell apoptosis to terminate systemic hyper-inflammation . This makes NGAL a promising therapeutic target in the management of gut-origin sepsis.