Table 1. Biosynthesis of secreted innate immunity proteins by hepatocytes.
| Innate Immunity proteins | Mainly synthesized in hepatocytes | Function | References | |
|---|---|---|---|---|
| Classical | C1r/s, C2, C4, C4bp | Activate C classical pathway | 13,14 | |
| Alternative | C3, B | Activate C alternative pathway | 13,14,15 | |
| Cs | Lectin | MBL, MASP1, 2 3, MAp19 | Activate C MBL pathway | 16,17,18 |
| Terminal | C5, C6, C8, C9 | Terminal C components | 13,14 | |
| Regulators | I, H, C1-INH | Inhibit C activation | 13 | |
| Opsonins | Pentraxins | CRP, SAP | Bind to microbes and subsequently activate Cs and phagocytosis to kill microbes | 19,20,21,35 |
| SAA | SAA | Binds to the outer membrane protein A family members on bacteria to activate phagocytosis | 24,25 | |
| LPS signaling regulators | Lipid transferase | LBP | Binds to LPS and subsequently transfers LPS to a receptor complex (TLR4/MD-2) via a CD14-enhanced mechanism | 51,52,53 |
| sCD14 | Soluble CD14 | Stimulates or inhibits LPS signaling depending on its concentration and environment | 54,55,56,57 | |
| sMD-2 | Soluble MD-2 | Stimulates or inhibits LPS signaling depending on its concentration and environment | 58,59 | |
| Iron metabolism | Iron-carrying protein | Transferrin | Binds to free iron, limiting iron availability to pathogens | 86 |
| -related proteins | Lipocalin-2 | Lipocalin-2 | Attenuates iron uptake by bacteria via binding to siderophores | 94,95,96,97 |
| Anti-microbial peptide | Hepcidin (also LEAP) | Anti-microbial peptide via limiting iron availability | 108,109 | |
| Hemopexin | Hemopexin | Retains heme from the bacteria by binding to heme | 103 | |
| Others | Clotting factors | Fibrinogen | A central regulator of the inflammatory response | 111 |
| PGRPs | PGLYP2 | Anti-inflammatory response via digestion of peptidoglycan on the bacterial wall | 160,161 | |
| Proteinase inhibitors | AAT, ACT, α1-CPI, α2M | Inactivate proteases released by pathogens and dead or dying cells | 124,125,126 | |
α1-CPI, α1-cysteine proteinase inhibitor (thiostain); α2M, α2-macroglobulin; AAT, antitrypsin; ACT, antichymotrypsin; B, factor B; C1-INH, C1 inhibitor; CRP, C-reactive protein; Cs, complements;, I, factor I; H, factor H; LBP, LPS-binding protein; LEAP, liver expressed antimicrobial peptide; MBL, mannan-binding lectin; MASP, mannan-binding lectin-associated serine proteases; PGRPs, peptidoglycan-recognition proteins; PGLYP2, peptidoglycan-recognition protein-2; SAA, serum amyloid A; SAP, serum amyloid P.