ABSTRACT
S iderocalin (lipocalin 2), first identified as a neutrophil granule component, is also found in uterine secretions, in serum and synovium during bacterial infection and secreted from epithelial cells in response to inflammation or tumorigenesis. Siderocalin is a po tent bacteriostatic agent in vitro and, when knocked-out in mice, confers a remarkable suscep tibility to bacterial infection in the absence o f any other phenotype. However, siderocalin lacked any precise function until specific, high-affinity ligands were identified: bacterial ferric siderophores. Siderophores, small-molecule iron (III) chelators, are synthesized, secreted and reabsorbed by microorganisms in a competition to obtain iron, a scarce resource in the envi ronment, and have been linked to virulence, though through previously undefined mecha nisms. Siderocalin employs degenerate molecular recognition machinery to bind to two dis tinct families o f siderophores: the catecholate siderophores o f enteric bacteria and the mycobacterial carboxymycobactins. Siderocalin therefore functions as an anti-bacterial com ponent of innate immune responses by sequestering iron away from invading pathogens; patho gens use siderophores that escape siderocalin capture to help establish virulence. However, the limited pattern of siderocalin siderophore specificity, the use of alternate or modified siderophores by bacteria and the possible existence of other siderophore-binding lipocalins (‘siderocalins’) clearly demonstrates that the batde for virulence is ongoing. Siderocalin may also have pleiotropic activities, having been implicated in diverse cellular processes such as apoptosis and differentiation.
