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This article comes from the official account of Wechat: ID:fanpu2019, author: Jon Lieff

The original title: "the soft cute character is a master, both a hero and a mole?" ? exhibition volume "

In the popular "working cells" of popular science, platelets are designed as cute young Loli images. They come on stage in groups when their blood vessels are damaged and come together to seal the wound to achieve the effect of stopping bleeding. But in fact, this is only the first understanding of platelets. Platelets, as a kind of "lower cells" without nuclei, and "higher cells" such as neurons, use the same language to participate in cell-to-cell dialogue and collective decision-making.

This article is an authorized excerpt from the Secret language of cells (September 2022 edition of Beijing United Publishing Company).

Write article | Jon Lieff

Translation | Gong Yin

Scientists were surprised to find that lower platelets, which are not even cells without nuclei, communicate meticulously with many other cells. Until recent discoveries, it has been thought that platelets are only part of large cells, and their only function is to clog and stop bleeding, occasionally clogging arteries because of the wrong caking position. Platelets can lead to heart attacks and strokes due to careless clots in the heart and cerebral vessels.

Until we discover the dialogue between platelets and immune cells, vascular cells and tissue cells, it is hard to imagine that platelets can function like cells. How do platelets produce signals and receptors? How to improvise without nucleus and DNA?

The answer is that platelets have been prepared long before they are separated from the mother cell "megakaryocyte", a large bone marrow cell. These mother cells provide platelets with a complete set of messenger RNA molecules encoded by their own DNA, as well as ribosome, a protein production machine. With all this support, platelets can compile complete signal and receptor information on their own.

Like the cellular dialogue that most immune cells engage in in the initial response to foreign enemies and injuries, platelet communication is important and diverse. Platelet signaling plays a key role in resisting microbes, and often leads the first batch of cells to fight with microbes in the body. With the advantage of numbers throughout the body, platelets can quickly find microbes and send messages to immune cells, stimulating them to activate defense mechanisms. While summoning white blood cells, platelets actively join the ranks of immune cells to fight infection. Platelets act as helpers for T cells, helping them guide B cells to produce better antibodies.

In addition to sending signals to immune cells to resist foreign enemies and fight microbes on their own, platelets have to solve another hemodynamic problem, which is "hemostasis", which is not as simple as thought. In the process of hemostasis, platelets must also respond to the exact blood flow needs of various tissues at the same time. Too much or too little blood flow can damage the tissue. If blood clots are excessive, blood clots can spread throughout the blood system, damaging multiple body areas at the same time. If the clotting is not enough, the tissue will bleed to death.

As the number one responder to injury, platelets must fight against microbes while immediately stopping bleeding and maintaining proper blood flow. When the tissue is damaged, microbes enter the tissue through trauma or foreign bodies. Tissue and vascular damage triggers multiple levels of clotting factors, which in turn guide platelets to change shape to form clots. Platelets also signal to attract immune cells to repair tissue and assist the formation of scab-forming scabs outside the cells. It can be said that platelets are involved in all the above activities at the same time.

Platelets, red blood cells and fibrin form a thrombus (electron microscope photo, David M. Phillips / Science Photo Gallery) A close look at platelets only mammals have platelets, and other creatures use different blood cells to do the same job. As mentioned earlier, platelets are produced by megakaryocytes in the bone marrow. In response to signals from the liver and kidneys, the megakaryocytes expand to 20 times their original size and immediately produce thousands of platelets. These platelets can survive for about a week. The mother cells of platelets start from the bone marrow, reach the spleen and store them for a rainy day. These cells are released under the stimulation of neuronal signals. Extensive cell-to-cell dialogue makes the supply of platelets exactly what is needed, but not so much as to oversupply.

Platelets can change their shape quickly because they are in a state of wrinkling, with a large number of extra cell membranes curled into wrinkles. Other cells send messages to platelets telling them when to change shape. The scaffold molecules inside the platelets respond to these messages, growing many long "arms" that stretch out from the platelet body. The platelet "metamorphosis" is divided into three stages: the new "arm" grows, the body stretches out and the central position thickens; at this time, the "generator" directly under the platelet membrane structure can rapidly expand the membrane surface area without the need to extend itself or add new materials. After that, the platelet's arm will attach to the ruptured blood vessel. Then, multiple platelets "hold hands" to form an embolic structure.

Platelets produce messages and aggressive molecules that are sent through vesicles containing chemicals. But platelets use vesicles to send messages only when the body grows from a circle to an "arm". Vesicles carry three signaling molecules, each of which plays a different role: one is used to regulate blood flow, the other is used to attach and kill microbes, and the third is used to reshape blood clots to repair damaged organs. To kill microbes, the platelet's arm must first catch the microbe and then inject it with vesicles. Platelets have so many receptors that they can sense each microbe, and platelets also provide specific toxic compounds that kill each microbe.

A full-scale attack of microbial platelets can sense the type and exact location of the injury and get there quickly. Because they are far more numerous than other blood cells, platelets are the first to account for the largest proportion of problem-solving participants, and they are also waiting for more powerful T cells and neutrophils to come to support. When microbes are found, platelets change shape and release aggressive molecules.

In order to fight microbes, platelets use a variety of techniques. When confronted with intractable bacterial species, platelets release a variety of vesicles, some containing phosphate energy particles and others containing proteins that can be used to attack microbes. Bacteria respond to attacks with their own signals, which prevent platelets from secreting and breaking down platelet proteins. Then, the platelets secrete some enzymes to break down the bacteria 'aggressive proteins. The confrontation will continue in many forms. For more information about the response of bacteria, see the third part of this book about microbes.

Secretions used by platelets to fight microbes can perform multiple functions at one time. Recent studies have found that an enzyme known to initiate the clotting process also cuts platelet products into fragments, each targeting specific microbial species. Another multifunctional molecule produced by platelets forms different fragments and modules as microbes change. these unique molecular regions send help signals to other cells in order to kill various types of microbes. When platelets directly attack microbes, the signal will mobilize a stronger attack.

Platelets also use special receptors in the fight against microbes. The internal receptor can sense the number of remaining aggressive molecules. When necessary, signals are sent from within, mobilizing messengers RNA and ribosomes to produce more aggressive molecules, sometimes a hundredfold. By using receptors, platelets can also analyze specific fat molecules protruding from cells, thus distinguishing human cell membranes from microbial cell membranes. On this basis, platelets can only attack microbes, not human cells.

A large number of platelet aggressive molecules can effectively fight a variety of microorganisms, including bacteria, fungi, protozoa and many viruses. Recent studies have shown that platelets are the first key line of defense against HIV (human immunodeficiency virus). Platelet factor has also been shown to limit streptococcal heart infection. A specific platelet molecule can enter red blood cells occupied by microorganisms and then attack the parasite that causes malaria, and the more platelets in the body, the greater the chance of success in the fight against malaria. In addition, platelets can also effectively fight a variety of fungi. To attack worms, platelets produce hydrogen peroxide and other aggressive molecules. Although platelets cannot "eat" microbes, they can block them and wait for larger macrophages to engulf them.

The most important function of helper immune cells platelets is likely to be to act as helper immune cells. They look at the surface of immune-clearing cells to determine which cells have been infected and can no longer fight microbes. Then send a signal to convey the results of their verification, summoning strong troops to fight. Platelets stimulate receptors that bind to microbes, making it easier for white blood cells to engulf microbes.

Platelets have a variety of immune signal receptors, which cause them to wander around the body in response to distant signals for help. After reaching the target location, platelets immediately use a large number of receptors and signals to deal with various types of cell damage. Some platelet signals cause white blood cells to react quickly, and platelets can also cause inflammation by using many of the most powerful immune signals. After evaluating the current situation, platelets send a series of messages as the situation changes. However, due to the complexity of the specific process, the signal sometimes goes wrong, which leads to the error of the clotting position.

Platelets can enhance the ability of white blood cells to engulf microorganisms. If it is determined that a strategy is necessary, the platelets will signal that certain types of clear white blood cells go to the location of fierce battle with the foreign enemy. The scavenging cells that gobble up the wreckage then produce enzymes that cut the molecules secreted by platelets into small fragments. This attack can only be effective under the combined action of platelet signals and scavenging enzymes. Microbes fight back with their own enzymes, trying to destroy the aggressive molecules of platelets. However, these enzymes can also inadvertently produce smaller fragments of platelet molecules, damaging the microbes themselves.

Neutrophils set traps for microbes, which we call "hunting nets". These nets are made up of DNA molecules and proteins. Platelets participate in the entire netting process, forming fiber aggregates with hunting nets and white blood cells. This complex structure can recruit and activate more immune cells. On this basis, platelet fibers can be more widely attached to microbial molecules in order to kill them. Hunting nets are a key attack mechanism that kills a variety of bacteria without damaging human tissue.

The auxiliary role of platelets is also reflected in other aspects. In order to solve the problem properly, powerful T cells need other cells to present microbial fragments or particles at the site of cell damage. Platelets themselves are not responsible for presenting substances to T cells, but they participate and enhance the specificity of the presentation process. To this end, platelets establish contact with microbes and quickly bind them to the presenting cells.

In the case of virus invasion, platelets will also send multiple activation signals directly to T cells. At the same time, platelets send signals that remind T cells to attack other infected cells. Platelets send signals as appropriate to summon the specific types of T cells needed. These platelet signals are also important for critical communication between T and B cells and contribute to the production of optimal antibodies.

The relationship between platelets and cancer cells and platelets is unique. As we will see in Chapter 8, cancer cells need to be supported by local tissue cells, immune cells, and vascular endothelial cells. Recent studies have found that platelets also help when cancer occurs. Platelets can use clotting and often use fibers to coat cancer cells to protect them from immune clearance cells and killer immune cells.

Platelets can assist in the construction of metastatic cancer community structure, and the more platelets in the community formation site, the worse the prognosis of the disease. Emerging treatments can play a role in solving the problem of platelet accumulation. In addition, another platelet signal triggers cancer cells to transform from passive cells that barely move into aggressive cells that move, causing malignant tumors to grow. In the absence of platelet signals, the invaded cancer cells may return to a more passive state, and the spread of cancer cells will stop.

Clots formed by platelets can promote the development of cancer, and cancer signals themselves can transform these clots into specific types, such as small clots, widespread dangerous clots, embolism that can damage the lungs, and so on. With the help of the dialogue between platelets and tissue cells, the wandering group of cancer cells can reach the distal tissue and begin to form new communities. Although each tissue in the body is different, platelets can use signals that are very unique to each tissue.

In addition, cancer and platelets interact in other ways. Cancer cell signals stimulate the dialogue between platelets and nearby tissue cells, which will win more support for cancer development in view of the existing relationship between platelets and these local cells. On the other hand, platelet signals also promote vascular leakage, making it easier for cancer cells to move in and out of the blood vessels.

It is inconceivable that platelets, a cell without nuclei, can do so much work.

A brief introduction to the author

Jon Liff (Jon Lieff), geriatric psychiatrist, distinguished lifelong fellow of the American Psychiatric Association, bachelor of mathematics from Yale University, M.D., Harvard Medical School. During his tenure as president of the American Geriatric Association (AAGP), he helped create the American Journal of Geriatric Psychiatry (American Journal of Geriatric Psychiatry), the core journal in the field of geriatric psychiatry. He is good at finding new targeted treatments for patients with brain injury and is a pioneer in this field.

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