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2015 ; 5
(126
): 104363-104374
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The Ligands of Neutrophil Gelatinase-Associated Lipocalin
#MMPMID27617081
Bao GH
; Ho CT
; Barasch J
RSC Adv
2015[]; 5
(126
): 104363-104374
PMID27617081
show ga
Neutrophil gelatinase associated lipocalin (NGAL), was originally identified in
neutrophil granules as a heterodimer complex with gelatinase B (matrix
metalloproteinase 9, MMP9), but more recently has been found to be secreted by
damaged epithelial cells. Ngal is a member of the lipocalin family and
subsequently named as lipocalin 2 on the basis of structural similarity with
other members of the lipocalin family and its potential association with
hydrophobic retinol and cholesterol oleate more strongly than their hydrophilic
counterparts. In 2002, a landmark paper suggested that Ngal is a bacteriostatic
agent which blocks iron acquisition by interacting with a number of bacterial
siderophores, especially enterobactin. Since then, more siderophore-carrying
functions have been reported than the possibility of hydrophobic ligand
transport. In this setting, Ngal was renamed Siderocalin. Functions of
siderocalin include not only bacteriostatic activity but potentially as a
mediator of cell growth and differentiation; some of these functions appear to be
referable to the holo siderocalin:siderophore:iron complex and recent work
suggests that metabolic products may act as mammalian siderophores bound by Ngal.
While still speculative, it may be that the mammalian siderophores can establish
the missing link between Ngal and a number of its functions in vivo. This review
provides an overview of the discoveries of the different ligands of Ngal and
consequently related functions. Hydrophobic ligands, bacterial siderophores as
well as their modified structures (synthetic siderophores), and mammalian
siderophores are summarized.