As the organisms’ complexity level increases, their immunity also becomes more extensive. Humans, for example, have various cells
Coming from the two Greek words “makro ” and “phagein ” which mean “big ” and “to eat ” respectively, macrophages[1] are large and specialized cells for destroying and engulfing foreign bodies. Check out the complete history of immunology
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 in the liver sinusoids are called Kupffer cells .
How to pronounce Kupffer Cells? Kupffer Cells 🔊 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%[2] 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 the “tolerogenic” phentotype[3] necessary to prevent undesired immune response to any stimuli.
They are identified to contain vacuoles and granules and tubular and vermiform (worm-like) invaginations.
Hepatic Structure (Source: Wikimedia) Discovery of Kupffer Cells [4] started when von Kupffer observed this so-called “Sternzellen ” (the German word for “star cells “) in the liver. By using the gold chloride staining technique, he thought that these cells have functions in 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[5] 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:
Phagocytosis (Source: Wikimedia – Modified to show legends) Anatomy of Kupffer Cell These cells are too minute to be observed individually using a compound microscope. Often, electron microscopy is to observe the Kupffer cells elongated to worm-like to the star-shaped body.
Like any other cells, they have various distributions 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 a 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 cytoplasm cellular respiration equation
Functions of Kupffer Cells Aside from digestion
1. To remove protein complexes and small particles from blood Together with other cells in the sinusoid endothelium, they are the first line of defense against pathogens
[6] entering the liver through the venous portal vein.
This function is important because the blood that passes through that vein is rich with pathogen-derived products like lipopolysaccharides and proteins. Such products must be removed from circulation to prevent systemic immune activation.
2. To capture and digest microorganisms and worn-out cells As macrophages, Kupffer cells can engulf and break down
[7] old red blood cells that pass through the liver sinusoids.
In addition, because of their peroxidase activity in the cytoplasm, they can degrade bacterial and other microorganism walls.
3. To modulate iron homeostasis in the liver A study published in the
Journal of Molecular Medicine (2008) [8] showed that Kupffer cells could control ion homeostasis through the exertion of regulatory signals for the expression of hepcidin.
Hepcidin is a peptide hormone that primarily controls the entry of iron in the circulatory system However, at present, that suppressing molecule produced by Kupffer cells is not yet identified.
4. To regulate anti-viral immunity during Hepatitis B and C infections A study published in the
Journal of Hepatology revealed that aside from their “
barrier ” and “
janitor ” function, they can also be used to inhibit the growth of viral infections in the liver, particularly 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 of how Kupffer cells mediate these infections remain unclear and are still up for further studies.
As mentioned above, Kupffer cells exhibit great adaptability depending primarily on their immune environment. But despite medical practices and technology advancements, understanding the exact mechanisms of their functions is still very rudimentary.
Hence, future studies should promote novel insights into the potential of Kupffer cells for therapeutic manipulation. Wouldn’t that be great?
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