Abstract
Background: LCN2 is a member of the lipocalin family that is expressed under pernicious conditions such as intoxication, infection, inflammation and cellular stress. Sustained LCN2 expression is induced in experimental liver injury. Immunohistochemistry and primary liver cell isolation identified injured hepatocytes as the main source of LCN2. Methods: LCN2-/- mice were used in experimental models (CCl4, BDL, LPS and ConA) for both acute and chronic liver injury. Liver function analysis, FACS-based liver leukocyte characterization, qRT-PCR for chemokine and cytokine expression and Western Blot as well as histology for fibrotic markers was performed. In addition, serum LCN2 from 91 control and 194 liver diseased patients was analyzed in ELISA. Results: Acute single dose CCl4 intoxication showed lipid droplet accumulation in hepatocytes in LCN2-/- mice. Liver leukocyte isolation showed CD45+ and CD11b+F4–80+ to significantly decrease in LCN2-/- mice, while we found no difference after 5 day BDL or during chronic CCl4 application or BDL for 4 weeks. In ConA models however, LCN2-/- mice showed slightly more liver damage and increased values of CD11b+F4–80+, CD45+ and Tregs than wild type animals. Although serum LCN2 levels in diseased humans were higher than in control patients, we found no difference between cirrhotic and non-cirrhotic patients. Patients with Child A and Child C showed higher LCN2 levels compared to control patients that were independent from disease etiology and serum AST and ALT. By contrast, serum LCN2 showed significant correlation with glomerular filtration rate. Conclusion: LCN2 is a fatty acid transport protein that mobilizes fatty acids from hepatocytes. LCN2-/- mice are unable to appropriately respond to acute CCl4 intoxication. LCN2 expression during inflammatory responses in liver depends on the chosen model. It acts as an acute-phase response protein but the expression during chronic liver insult does not correlate to AST and ALT.
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