Studies of the release and turnover of a human neutrophil lipocalin

Abstract

A 24-kDa protein was purified from human neutrophil extracts and shown to be the newly discovered neutrophil gelatinase-associated lipocalin (NGAL), based on structural and immunochemical data. A specific enzyme-linked immunosorbent assay (ELISA) was developed for the determination of NGAL in human plasma and tissue fluids. Normal human plasma contains 72 micrograms l-1 of NGAL (range 40-109 micrograms l-1) in two main forms, monomer and dimer. 35S-methionine metabolic studies of human neutrophils showed that granulocyte macrophagecolony-stimulating factor (GMCSF) stimulated significant synthesis and secretion of NGAL in a dose- and time-dependent fashion. NGAL was rapidly released as monomer and dimer on incubation of heparinized whole blood with opsonized yeast, reaching a plateau corresponding to about 35% of total cell content after 30 min. Following intravenous injection of 125-iodine labelled NGAL there was a more rapid initial clearance of the monomeric than of the dimeric form; t1/2 10 min vs. 20 min. During the second phase the two forms cleared at similar rates. Severe acute peritonitis was accompanied by a 10-fold increase in NGAL plasma levels and the NGAL level in peritoneal exudates, which reached about 40 mg l-1. There was a good linear correlation between the concentrations of NGAL, leucocyte elastase and NP4 (neutrophil proteinase 4 = P3).

Factors limiting usefulness of serum and urinary NGAL as a marker of acute kidney injury in preterm newborns

“…1 NGAL has short half-life, estimated at 10-20 min due to rapid elimination from circulation by the kidney. 3 It is postulated that increased serum NGAL (sNGAL) and urinary NGAL (uNGAL) is a sensitive marker of acute kidney injury (AKI), predominantly of tubular cell damage, not related to glomerular filtration decline. 4,5 Additionally, it was shown that NGAL is a marker of neutrophil activation and the severity of sepsis in populations other than newborns.…”

“…[1][2][3] The major biological role of this 24 kDa protein is iron-chelating, preventing its uptake by microorganisms. 1 NGAL has short half-life, estimated at 10-20 min due to rapid elimination from circulation by the kidney.…”

Neutrophil Gelatinase-Associated Lipocalin: A New Biomarker for COPD Acute Exacerbation

“…There are only a limited number of studies investigating the value of NGAL on acute infections. In the study conducted by Axelsson et al it was seen that serum NGAL level was 10 times higher in patients with acute peritonitis compared to control group [18]. In another study carried out by Chakraborty et al serum NGAL levels were higher in patients with acute pancreatitis in relation to severity of the disease [9].…”

Identification of Factors Causing Sudden Coagulation in Patients with Acute Myocardial Infarction

“…As IL-8 stimulates from human neutrophils [22] the release of NGAL [23] and MMP-9 [25,26] affecting coagulation [14,15], the observed IL-8 increase suggests that this factor may be involved in facilitating the coagulation process.…”

“…It is important to remember that IL-8 exhibits the capacity to recruit the neutrophils [22] that releases NGAL [23], sorted to azurophil granules [24]. In addition, as IL-8 stimulates from human neutrophils [22] the release of NGAL [23] and MMP-9 [25,26] affecting coagulation [14,15], the IL-8 increase, observed, suggest that this factor may facilitate the coagulation process. High values of IL-8 or other chemokines can be used to predict cardiovascular risk [27], and indicate a probable future CAD in normal subjects [28,29].…”