Tear lipocalin: structure, function and molecular mechanisms of action.

Human tear lipocalin (TL), or von Ebner's gland protein, accounts for about 15-33% of the protein in tears. I-4 TL has been identified in lacrimal gland, von Ebner' s gland, prostate, nasal and tracheal mucosa and skin.512 TL was recognized as a member of the lipocalin family when its primary sequence was determined.7.I3 .14 Lipocalins form a functionally diverse group of proteins with extremely varied amino acid sequences. yet some similar structural properties (Fig. 1). Eight strands (A-H) are arranged in aß-barrel and are joined by loops between the ß-strands. 15-19 Many of the lipocalins, including TL, are believed to function as dimers. 20. 21 There are highly conserved regions that are important to ligand affinity and lipocalin stability. Most lipocalins have 1-3 disulfides bonds and one in particular is conserved and may play a role in modulating ligand binding. 15. 22 A completely conserved tryptophan on the Astrand is implicated in ligand binding and prevention of oxidation of retinol, as weIl as protein stability of various lipocalins.23.24 A variety of general functions for TL have been suggested based on its binding of lipid molecules. These include the binding and transport of phospholipids, fatty acids, cholesterol, retinol, tocopherol, and tastants, the scavenging of harmful lipids such as phthalates and lipid products of inflammation, antimicrobial activity, or capture of fatty acids that inhibit antimicrobial activity, endonuclease activity, and cysteine proteinase inhibition.6.7.25-33