Generally speaking, hepatocytes are a type of cell found in the liver. They are responsible for the production of proteins known as innate immunity proteins. They also help in the breakdown of bilirubin and help excrete biliary fluid.

Innate immunity proteins produced by hepatocytes

During a viral or bacterial infection, the natural immune response plays an essential role in defending the host. Hepatocytes are essential in producing acute-phase proteins participating in the innate immune response. Hepatocytes are also responsible for producing complement proteins that act as regulators of the immune response. In addition to complement, the liver also has a variety of plasma complement components. Hence we must learn about hepatocytes structure to better understand how they work.

The innate immune system relies on recognizing a variety of nonself molecules. In particular, the recognition of bacteria and PAMPs occurs in the peripheral blood. Several hepatocyte-derived natural immunity proteins contain binding sites for liver-enriched transcriptional factors. These proteins have been shown to activate the inducible expression of innate immunity proteins in hepatocytes. In addition, many complement proteins are further upregulated after a bacterial infection.

The hepatic reticuloendothelial system is essential for removing bacterial circulating microorganisms. Hepatic NK cells and liver-specific endothelial cells comprise this system (LSECs). The start of an immune response and the control of bacterial infection depend heavily on these cells.  Numerous soluble pattern-recognition receptors (PRRs) produced by the liver stimulate the complement system. Innate immunity is triggered by a peptidoglycan-recognition protein found in the liver.

Endocytic mechanisms found in hepatocytes

Hepatocytes, the most abundant cells in the liver, are involved in several physiological processes. These include steroid hormone metabolism, bile secretion, detoxification, and glycogen metabolism. In addition, hepatocytes play a vital role in the metabolism of lipids, carbohydrates, and lipid-based drugs. The hepatocyte has a complex network of endocytic pathways. This complex network helps the cell to internalize various ligand complexes. It also regulates the uptake of pathogens and trophic factors. In addition, hepatocytes are responsible for the metabolism of steroid hormones and lipids.

In addition to the internalization of ligands, the cell also communicates with the adjacent cells. In this process, the hepatocytes release large amounts of EVs. These EVs have biologically active components and can promote inflammation and metabolic reprogramming. Different types of EVs have been shown to affect different pathways. These pathways include receptor-mediated endocytosis and clathrin-mediated endocytosis. These two endocytic pathways are also critical in the metabolic reprogramming of hepatocytes. The lipid and protein components of these NPs are essential for their function. However, the exact mechanisms by which these NPs are taken into the cell still need to be determined.

Bilirubin breakdown

Besides being a diagnostic indicator of liver disease, bilirubin is also used as supportive evidence for hemolytic anemia. The catabolism of various hepatic hemoproteins produces approximately 20% of bilirubin. The other half is made from inefficient erythropoiesis in the bone marrow. Bilirubin is a brownish-yellow pigment present in the bile. It is formed from the breakdown of heme, an iron atom surrounded by four pyrroles. In the endoplasmic reticulum, bilirubin is conjugated with glucuronic acid. The conjugated bilirubin then enters the intestine and is safely eliminated through the excretion into the bile. Bilirubin is considered to be an essential detoxification mechanism.

The liver and kidney metabolize bilirubin. In the liver, hepatocytes break down bilirubin into free bilirubin and glucuronic acid. Hepatocytes reabsorb these bilirubins. Hepatocytes can then excrete the conjugated bilirubin into the bile or back into the blood. This process involves the disruption of the hydrogen bonds that hold bilirubin in its water-soluble form.


Hepatocytes are also involved in the adaptive immune system. They respond to pathogenic signals and cytokines present in the blood. They secrete various innate immunity proteins, including bactericidal and iron metabolism-related proteins, to protect the host from infection. They also produce IL-1b, which augments the expression of many innate immunity proteins in the hepatocytes. Hepatocytes also have SMD-2, which acts as an opsonin to promote bacterial clearance.

A system-scale stoichiometric model of human hepatocyte metabolism is critical to understanding the hepatocyte’s metabolism. It is based on a comprehensive evaluation of the metabolic activities of the hepatocytes. The model can achieve all biochemical and physiological objectives in parallel. It is expected to provide a structural framework for computational studies on the functions of the liver. A genome-scale metabolic network of the human hepatocytes (HepatoNet1) was developed and evaluated for its capacity to accomplish various metabolic objectives. The network was based on two global reconstructions of the human metabolic network.

Endocytic mechanisms

The functions of internalization and metabolism of substances remain unclear. To better understand the endocytic pathways, scientists have developed improved imaging techniques. They have gained detailed insight into hepatocyte endocytic mechanisms. This system provides tight spatial regulation of vesicle formation.

External signals, pathogens, and viruses can trigger the endocytic pathway. For example, HBV infection hijacks endocytic pathways. These pathways can lead to steatotic conditions in the liver. Hepatocytes use a variety of endocytic mechanisms to maintain normal lipid serum levels. The clathrin coat is a protein complex that is regulated by Rab GTPases. These proteins control the clathrin coat assembly and the cargo’s attachment.