A 25 kDa α₂‐microglobulin‐related protein is a component of the 125 kDa form of human gelatinase

Abstract

Besides the mnnomcric mammalian 95 kDa progelatinase, two additional forms, ~1 disulfide-bridged 220 kDa dinxr and a 125 kDn form were isolated from human PMN Icukocytes. The I25 kDa progelatinase was identified as a covalcntly linked, disul!!de-bridged hetcrodimer formed of the monomer with a 2s kDa protein. This 25 kDa protein was isolntcd from pclatinase bound to the atIinity support of gelatin-Scpharosc and eluted by DTE-containing bulli3r. The amino acid sequence of tryptic peptides of this protein rcvenled homology with an c+-microglobulin-related protein from rats, a protein so far unknown in humans.

The lipocalin protein family: structure and function

“…Are the allergenic properties of several, evolutionarily distinct lipocalins [6] merely a co-incidental property of their individual structures, or do they result from conserved structural features, such as the ability to interact with cellular receptors, common to the family ? Can the immunosuppressive and cell-regulation functions of the family be linked to macromolecular complexation, perhaps through the modulation of proteinase-mediated cell signalling [137], either by the down-regulation of protease inhibitors [50] or by the direct inhibition of proteases themselves [42] ? The immunosuppressive and cell-regulatory properties of the lipocalins suggests that they might be examined as candidates for protein therapeutics.…”

“…Tumour necrosis factor-α can regulate NGAL expression in cultured liver cells. These findings indicate that NGAL is a positive APP and may possess immunosuppressive or anti-inflammatory properties, possibly linked to its regulation of neutrophil gelatinase or other plasma protein [42]. The uterus is also a major site of NGAL synthesis, especially at parturition, when expression increases significantly, suggesting a physiological role for the protein in uterine secretions [104].…”

“…More recently, it has been shown that neutrophil lipocalin (NGAL) is covalently attached to human neutrophil gelatinase (type IV collagenase) via an intermolecular disulphide [42,43], although most of the protein is secreted in an uncomplexed form. These authors propose a regulatory role for NGAL on the action of gelatinase.…”

Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression

“…Lcn2 is a multifunctional 25-kDa protein that has roles in innate immunity and tumourigenesis. Also known as neutrophil gelatinase-associated lipocalin (NGAL), Lcn2 is now recognized as an adipokine as it is predominantly produced by white adipose tissue [19]. Lcn2 has recently been identified in growth plate chondrocytes [20] where expression is modulated by IL-1b, leptin, adiponectin, lipopolysaccharides, and dexamethasone.…”

Expression, purification, crystallization and crystallographic characterization of dimeric and monomeric human neutrophil gelatinase associated lipocalin (NGAL)

“…of a disulfide-linked heterodimer secreted by neutrophils (Triebel et al, 1992;Kjeldsen, Johnsen et al, 1993). Gelatinase is a neutral metalloproteinase which has been isolated from neutrophils, macrophages and fibroblasts that degrades a number of the components of the extracellular matrix.…”