Human tear lipocalin (TL; also known as Lcn1) is a secretory protein present in large amounts in fluids that cover epithelial surfaces such as tears and respiratory secretions. It is supposed to act as a physiological scavenger of hydrophobic, potentially harmful molecules, but there is evidence that it also inhibits bacterial growth. In the present study, we reconsidered the possibility that TL might interfere with microbial growth by scavenging of siderophores, as described for human neutrophil gelatinase-associated lipocalin (NGAL). Indeed, our experiments revealed that TL binds to microbial siderophores with high affinities. In contrast to NGAL, which was shown to have some specificity for bacterial catecholate-type siderophores, TL binds to a broad array of siderophores, including bacterial catecholate-type enterobactin and hydroxamate-type desferrioxamine B, and all major classes of fungal siderophores. By adding exogenous TL, bacterial and fungal growth could be inhibited under iron-limiting conditions. Thus, TL might be a novel member of the innate immune system especially involved in mucosal defense against fungal infections.

beta-Lactoglobulin (BLG) is a member of the lipocalin protein family and a major food-borne allergen in humans. Numerous in vitro studies have suggested a role for BLG in molecular transport processes; however, its physiological role remains enigmatic. A cellular receptor for BLG has been proposed, but has not yet been identified. Here we show that human LIMR, known to act as an endocytic receptor for lipocalin-1, also binds bovine BLG and mediates its cellular uptake. The specificity of this interaction is corroborated by a complete block of cellular uptake of BLG in the presence of LIMR antibodies or LIMR downregulation by antisense RNA. Furthermore, heterologous expression of human LIMR in insect cells mediates cellular internalization of FITC-BLG. Since LIMR is highly expressed in the human intestine, it might also function in the uptake of food-borne BLG.