Kupffer Cells: Every day living organisms like humans are subject to the attack of disease-causing agents called pathogens. The only good thing is that they have a special kind of innate protection referred to as “immunity“.
As the level of the complexity of the organisms increase, their immunity also becomes more extensive. Humans, for example, have various cells in the body which act to help deter the presence of pathogens.
Coming from the two Greek words “makro” and “phagein” which mean “big” and “to eat” respectively, macrophages are large and specialized cells for destroying and engulfing foreign bodies. Check out the complete history of immunology and its timeline here.
They are usually formed as a response to an infection or an accumulation of dead and damaged cells. Interestingly, macrophages in the body are modified to different structures and forms to adapt to various microorganisms and invaders.
For instance, macrophages located in the liver sinusoids are called Kupffer cells.
How to pronounce Kupffer Cells?
| Word Origin: German |
What are Kupffer Cells?
In mammalian bodies, Kupffer cells are the most abundant tissue macrophages as they constitute 80-90% of them. Also known as Kupffer-Browicz cells or stellate macrophages; these specialized macrophages are specifically found in the liver.
As identified in the early 1970s, the specialized function of Kupffer cells is mainly due to their peroxidase activity. In biology, this is termed as the “tolerogenic” phentotype necessary to prevent undesired immune response to any stimuli.
They are identified to contain vacuoles and granules and tubular and vermiform (worm-like) invaginations.
Discovery of Kupffer Cells
First described in 1876, they were named after the German scientist Karl Wilhem von Kupffer. This discovery started when von Kupffer observed this so-called “Sternzellen” (German word for “star cells“) in the liver. By using gold chloride staining technique, he thought that these cells have functions in the the tissue called space of Disse (perisinusoidal connective tissue in liver blood vessels).
Twenty-two years later, such an idea was disproved by scientist Tadeusz Browicsz as he correctly identified them as macrophages.
Development of Kupffer Cells
In humans and other mammals, the development of Kupffer cells starts in the yolk sac. Primitive macrophages differentiate into fetal macrophages and then enter the bloodstream. After that, they go to the fetal liver to become mature cells.
Here is an overview of Phagocytosis:
Anatomy of Kupffer Cell
These cells are too minute to be observed individually using a compound microscope. Oftentimes, electron microscopy to observe the Kupffer cells elongated to worm-like to the star-shaped body.
Like any other cells, they have various distribution and arrangements of organelles. Described below are some of them.
Plasma Membrane
They have plasma membranes with extensions like microvilli, pseudopodia, filopodia, and lamellipodia. These structures are what give them the star-like to worm-like appearance.
Cytoplasm
They are the largest sinusoidal cells, hence, their cytoplasmic volume is generally dense and considerable. Aside from that, their cytoplasm contains a large number of lysosomes (for degradation of organelles and removal of wastes), vacuoles (storage of materials and wastes ), and phagosomes (involved in the engulfment of foreign bodies).
Golgi Bodies
In Kupffer cells, the Golgi bodies are seen observed to be in groups near the nucleus. In the cell, the Golgi bodies are involved in the secretion and intracellular transport of vesicles.
Rough Endoplasmic Reticulum (RER)
Known to be the organelle responsible for ribosome (for protein synthesis) synthesis, the rough ER is very abundant in Kupffer cells.
Nucleus
Like most animal cells, they contain only a single nucleus. Their nuclei are mostly oval-shaped and have finely distributed euchromatin. It is the nucleus that contains the genetic information which is responsible for the expression of traits.
Other Organelles
Other organelles like the free ribosomes (for protein synthesis), mitochondria (for ATP/ energy production), and microtubules (for the transport of other organelles) are simply dispersed in the cytoplasm. Check out the cellular respiration equation here. Unlike other liver cells, Kupffer cells do not contain glycogen and fat droplets.
Functions of Kupffer Cells
Aside from digestion, detoxification, and storage, the liver can function for immunity through the Kupffer cells. The following are ways on how such cells contribute to immune function.
1. To remove protein complexes and small particles from blood
- This function is important because the blood that passes through that vein is rich with pathogen-derived products like lipopolysaccharides and proteins.
- Such products need to be removed in the circulation so as to avoid systemic immune activation.
2. To capture and digest microorganisms and worn-out cells
- In addition to that, because of their peroxidase activity in the cytoplasm, they can also degrade bacterial and other microorganism walls.
3. To modulate iron homeostasis in the liver
- Hepcidin is a peptide hormone that primarily controls the entry of iron in the circulatory system of mammals. Interestingly, when hepcidin levels increase (especially during an inflammation or an immune response), serum iron and the absorption of iron in the gut decreases.
- However at present, that suppressing molecule produced by Kupffer cells are not yet identified.
4. To regulate anti-viral immunity during Hepatitis B and C infections
- Together with other macrophages, they contribute to the tissue damage of the infected body part. Aside from that, they also regulate fibrosis (thickening of connective tissue), cirrhosis (scarring of the liver), and hepatocellular carcinoma (abnormal growth of liver cells), which all happen during hepatitis.
- However the exact mechanisms on how Kupffer cells mediate to these infections still remain unclear and is still up for further studies.
As mentioned above, Kupffer cells exhibit great adaptability depending primarily on their immune environment. But despite the advancement of medical practices and technology, understanding the exact mechanisms of their functions is still very rudimentary.
Hence future studies should be geared toward promoting novel insights into the potential of Kupffer cells for therapeutic manipulation. Wouldn’t that be great?
