The cells in the liver, called kupffer cells, are the first line of defense against infections and play a crucial role in immune function. They are responsible for forming macrophages, the primary body cells that attack viruses, bacteria, and other pathogens. When activated, the resulting immune responses can damage the cells of the liver. A common cause of hepatic fibrosis is an accumulation of these immune cells in the hepatocytes, which are the liver cells that produce enzymes.
Activation
Kupffer cells are essential mediators of liver repair. They initiate the recruitment of monocytes to the site of injury. The activated Kupffer cell also contributes to the liver’s progression of fibrosis and cirrhosis. However, the role of Kupffer cells during liver damage is complex.
kupffer cells in the liver are the critical hepatocyte progenitor cells that produce hepato-protective cytokines, such as tumor necrosis factor-alpha, interleukin-1b, and transforming growth factor-beta 1. In addition, Kupffer cells are also crucial in activating hepatic stellate cells, which synthesize ECM proteins. As a result, the interaction of these two cell populations is essential for the healing process.
A wide range of conditions requires the activation of Kupffer cells. Some states involve a hepatotoxic agent, such as alcohol and acetaminophen, while others involve a metabolic disease, such as chronic hepatitis C or diabetes. In some cases, the activity of these cells can suppress the systemic immune response. Hence, it is critical that therapeutic strategies to modulate the activity of Kupffer cells be timed and appropriately targeted.
Formation of macrophages
Macrophages play a vital role in physiologic homeostasis. They can respond to various stimuli, from immunologically derived molecules to low molecular metabolite products. In addition, macrophages contribute to hosting defense. However, macrophages also contribute to fibrosis, a common clinical manifestation of chronic injury.
Macrophages in the liver are essential for liver function. These cells undergo various changes during inflammation and fibrosis. The production of cytokines regulates this process. In addition, the macrophages secrete a variety of mediators, which activate intracellular inflammasomes and release IL-1b.
There are several different macrophage types, which can be distinguished based on gene expression and phenotypic characteristics. During the development phase, macrophages are formed from embryonic precursors. They can then be differentiated into tissue macrophages. Macrophages are found in various organs, including the liver, brain, and kidneys. Their functions vary, depending on the organ.
Hepatic macrophages are divided into two groups according to Ly-6C expression. These are restorative macrophages and profibrotic macrophages. A restorative macrophage is a monocyte-derived macrophage that accumulates in the liver. Its ancestry can be traced to the Ly-6Chi monocytes recruited to the liver in acute inflammation.
Hepatotoxicity
Kupffer cells are a group of macrophages that play an essential role in liver homeostasis. They interact with many liver cellular components. For example, in response to injury, they release pro-inflammatory cytokines that activate the hepatocyte. These include tumor necrosis factor (TNF), interleukin-1beta, CCL2, and TNFa.
The liver contains a heterogeneous population of non-parenchymal cells (NPCs). This population comprises resident Kupffer cells, Ly-6C+ macrophages, and NPCs. Each population displays a different function.
Resident Kupffer cells play a critical role in hepatocyte recruitment during the initial phase of injury. Kupffer cells rapidly produce cytokines such as IL-1b, TNFa, CCL2, and chemokines. In addition, activated Kupffer cells also initiate the recruitment of monocytes.
Monocytes participate in hepatocyte trans-differentiation and reversion, as well as fibrosis resolution. Toll-like receptors (TLRs) play a significant role in determining the fate of these activated cells.
Kupffer cells and HSCs are essential in the pathogenesis of acute and chronic liver diseases. During liver injury, these two populations interact to influence the balance between mechanisms of progression and resolution.
Antigen-presenting function
Kupffer cells are macrophages that are found in the liver. They are an essential part of the innate immune response. Some studies suggest they may participate in the pathogenesis of several liver diseases.
These cells play an essential role in host homeostasis, as they clear and degrade bacteria, viruses, and parasites. They also regulate metabolic function and immune modulation. However, their exact parts could be more precise.
Activation of these cells can be either paracrine or autocrine. Depending on the activation mechanism, they can differentiate into M1 or M2-like macrophages. In pathological conditions, Kupffer cells also produce inflammatory cytokines.
Kupffer cells are effective antigen-presenting cells (APCs) in vitro. In addition, they also appear to be a significant source of chemoattractant molecules for CD8 T cells. Although there are several theories about the origins and functions of Kupffer cells, the underlying mechanisms are still unclear. Nevertheless, some evidence from animal models indicates that they may contribute to the pathogenesis of various liver diseases.
Kupffer cells are also believed to contribute to alcohol-related liver disease. Alcohol-related liver disease is characterized by chronic inflammation and alcoholic fibrosis, which leads to alcoholic cirrhosis.
Hepatic fibrosis
Hepatic macrophages are a group of non-parenchymal cells that play a vital role in the pathogenesis of liver disease. These cells have many essential functions in host homeostasis and metabolic processes. In addition, they play a critical role in the immune system. Various research studies have been conducted on hepatic macrophages.
These cells are found in healthy livers. They are known to be activated by pro-inflammatory cytokines and are involved in the inflammatory response. Some studies have focused on the functional and phenotypic heterogeneity of hepatic macrophages. The context of injury mainly influences this heterogeneity.
During acute injury, Kupffer cells are found in higher numbers. They are responsible for clearing pathogens and debris from the liver. In addition, these cells are a significant source of pro-inflammatory cytokines. The release of these molecules is triggered by the release of damage-associated molecular patterns (DAMPs). DAMPs can be intracellular proteins, nucleic acids, or mitochondrial compounds. Once released, these molecules send out danger signals to surrounding cells.
After the initial influx of pro-inflammatory cytokines, macrophages switch to an anti-inflammatory phenotype. They secrete TGF-b, IL-10, and IL13. They also produce chemokines. These chemokines facilitate the migration of monocytes to the injured liver.
