Chapter 3. Monocytes and macrophages

Monocytes and macrophages are the main cells of the phagocytic mononuclear system (WHO) or the macrophage system of I. I. Mechnikov.

Monocytes originate from granulocyte-monocytic progenitor cells, macrophages - from monocytes passing from the bloodstream to tissue. Macrophages are present in all kinds of tissues. the human body: in the bone marrow, in connective tissuein the lungs (alveolar macrophages), in the liver (Kupffer cells), in the spleen and lymph nodes, in serous cavities (abdominal cavity, pleural cavity, pericardial cavity), in bone tissue (osteoclasts), in the nervous tissue (microglial cells), in the skin (Langerhans cells). They can be both free and fixed. In addition, dendritic cells (having a large number of short branching processes) present in all tissues also belong to macrophage elements. During numerous bone marrow transplant operations from a donor of a different sex, the hematopoietic origin of alveolar macrophages, Kupffer cells, Langerhans cells and osteoclasts was proved.

Having formed in the bone marrow, the monocyte is there for 30 to 60 hours. After that, it divides and enters the systemic circulation. The period of circulation of the monocyte in the blood is approximately 72 hours, where it ripens. The nucleus of the monocyte is transformed from round to first bean-shaped, and then to the cinquefoil. In addition, there is a change in the structure of the genetic material of the cell. The color of the cytoplasm of a monocyte can be completely different - from basophilic to gray-blue or even pinkish. After exiting the bloodstream, the monocyte can no longer return to the systemic circulation.

Macrophages located in various tissues of the human body have a number of common features. In the study of alveolar macrophages, it was found that tissue macrophages maintain their population not only due to the formation in the bone marrow, but also due to their ability to divide and self-maintain. This distinguishing feature macrophages becomes apparent in the case of suppression of the formation of these blood cells in the bone marrow under the influence of radiation or drugs with a cytostatic effect.

The nucleus of the macrophage is oval. The cytoplasm of the cell is large enough, does not have clear boundaries. The diameter of the macrophage normally varies widely: from 15 to 80 microns.

Specific functional features of macrophages are the ability to adhere to glass, the absorption of liquids and more solid particles.

Phagocytosis is the “devouring” of foreign particles by macrophages and neutrophils. This property of body cells was discovered by I. I. Mechnikov in 1883; he proposed the indicated term. Phagocytosis consists of the capture by a cell of a foreign particle and its confinement in the vesicle - the phagosome. The resulting structure moves deeper into the cell, where it is digested with the help of enzymes released from special organelles - lysosomes. Phagocytosis is the most ancient and important function of macrophages, due to which they rid the body of foreign inorganic elements, destroyed old cells, bacteria, as well as immune complexes. Phagocytosis is one of the main body defense systems, one of the links of the immune system. In macrophages, its enzymes, like many other structures, are subordinate to the role of these blood cells in immunity and, first of all, to phagocytic function.

Currently, more than 40 substances produced by the microphage are known. The enzymes of monocytes and macrophages that realize the digestion of the formed phagosomes are peroxidase and acid phosphatase. Peroxidase is found only in cells such as monoblasts, promonocytes and immature monocytes. In the cells of the last two stages of differentiation, peroxidase is present in very small quantities. Mature cells and macrophages, this enzyme, as a rule, do not contain. The content of acid phosphatase increases during the maturation of monocytes. Its greatest number is in mature macrophages.

Of the surface markers of monocytes and macrophages, immune phagocytosis is facilitated by receptors for the Fc fragment of immunoglobulin G and the complement component C 3. Using these markers, immune complexes, antibodies, various blood cells coated with antibodies or complexes consisting of antibodies and complement are fixed on the surface of monocyte-macrophage cells, which are then drawn into the cell carrying out phagocytosis and digested or stored in phagosomes.

In addition to phagocytosis, monocytes and macrophages have the ability to chemotaxis, i.e., are able to move in the direction of the difference in the content of certain substances in cells and outside cells. Also data blood cells they can digest microbes and produce several complement components that play a leading role in the formation of immune complexes and in the activation of antigen lysis, produce interferon that inhibits the multiplication of viruses, and secrete a specific lysozyme protein with a bactericidal effect. Monocytes and macrophages produce and secrete fibronectin. This substance is in its chemical structure a glycoprotein that binds the products of cellular decay in the blood, plays an important role in the interaction of the macrophage with other cells, in the attachment (adhesion) of the elements to be phagocytosed on the surface of the macrophage, which is associated with the presence of fibronectin receptors on the macrophage membrane.

The macrophage's protective function is also related to its ability to produce endogenous pyrogen, which is a specific protein that is synthesized by macrophages and neutrophils in response to phagocytosis. Standing out from the cell, this protein affects the center of thermoregulation located in the brain. As a result, the body temperature set by the indicated center rises. Due to the action of endogenous pyrogen, an increase in body temperature contributes to the body's fight against an infectious agent. The ability to produce endogenous pyrogen increases as macrophages mature.

The macrophage not only organizes a system of nonspecific immunity, which consists in protecting the body from any foreign substance or cell, extraneous to this organism or tissue, but also directly involved in a specific immune response, in the "presentation" of foreign antigens. This function of macrophages is associated with the existence of a special antigen on their surface. HLA-DR protein plays a decisive role in the development of a specific immune response. In humans, there are 6 variants of the HLA-DR-like protein molecule. This protein is present in almost all hematopoietic cells, starting from the level of pluripotent precursor cells, but is absent on mature elements of a hematopoietic nature. HLA-DR-like protein is detected in endothelial cells, sperm, and many other cells of the human body. On the surface of immature macrophages, found mainly in the thymus and spleen, an HLA-DR-like protein is also present. The highest content of such a protein was found on dendritic cells and on Langerhans cells. Such macrophage cells are active participants in the immune response.

A foreign antigen entering the human body is adsorbed by the surface of the macrophage, absorbed by it, appearing on the inner surface of the membrane. Then the antigen is cleaved in the lysosomes. Fragments of the cleaved antigen exit the cell. Some of these antigen fragments interact with the HLA-DR-like protein molecule, resulting in a complex on the surface of the macrophage. Such a complex releases interleukin I, which enters the lymphocytes. This signal is perceived by T-lymphocytes. Amplifier T-lymphocytes have a receptor for an HLA-DR-like protein associated with a fragment of a foreign antigen. Activated T-lymphocytes secrete a second signaling substance - interleukin II and growth factor for lymphocytes of all types. Interleukin II activates helper T-lymphocytes. Two clones of this type of lymphocytes respond to the action of a foreign antigen, producing a B-lymphocyte growth factor and a B-lymphocyte differentiation factor. The activation of B lymphocytes results in the production of immunoglobulin antibodies specific for this antigen.

Thus, although recognition of a foreign antigen is a function of lymphocytes without the participation of a macrophage that digests the antigen and combines part of it with an HLA-DR-like surface protein, it is impossible to present the antigen to lymphocytes and the immune response to it.

Macrophages have the ability to digest not only bacterial cells, red blood cells and platelets, on which some complement components are fixed, including aging or pathologically altered, but also tumor cells. This type of macrophage activity is called tumorucidal. From this we cannot conclude that the macrophages actually fight the tumor, namely, “recognition” of such type of cells as foreign tissue, due to the fact that in any tumor there are a lot of aging cells that are subject to phagocytosis similar to all non-tumor aging cells.

Certain factors produced by cells of a monocytic-macrophage nature (for example, prostaglandins E, lysozyme, interferon) are involved in both immune function and hematopoiesis. In addition, macrophages help the development of an eosinophilic reaction.

The macrophage nature of osteoclasts is proven. Macrophages are able, firstly, to directly dissolve bone tissue, and secondly, to stimulate the production of osteoclast-stimulating factor T-lymphocytes.

This function of macrophages may be leading in the pathology caused by tumor and reactive proliferation of macrophages.

Macrophages play a very significant role in the constancy of the internal environment. First of all, they are the only cells that produce tissue thromboplastin and trigger a complex cascade of reactions that ensure blood coagulation. However, it is likely that the increase in thrombogenic activity due to the activity of macrophages can also be due to the abundance of both secreted by them and intracellular secreted during the decay of cells, proteolytic enzymes, and the production of prostaglandins. At the same time, macrophages produce plasminogen activator, an anticoagulant factor.

Macrophages - what kind of creatures are they? Or formations? What are they responsible for in our body? These, as well as a number of similar questions, will be answered in the framework of the article.

general information

Mononuclear phagocytes (or macrophages) are a group of long-living cells that are capable of phagocytosis. They have quite a few common functions that make them related to neutrophils. Macrophages are also active participants in complex inflammatory and immune reactions, where they act as secretory cells. How do they function? Macrophages, like neutrophils, leave the vascular bed by diapedesis and begin to go their own way - to circulate in the blood. But they are sent to the fabric. After this, the transformation of monocytes → macrophages occurs. And already at the place of arrival, they will perform their specific functions, which depend on the anatomical location. This applies to the liver, lungs, bone marrow and spleen. In them, they will be engaged in the removal of harmful particles and microorganisms from the blood. What can they “turn into"? Kupffer and microglia cells, alveolar macrophages, macrophages of the spleen, lymph nodes, bone marrow - this is what they are transformed into.

Functional

The body’s macrophages have two main functions, which are performed by different types:

1. Elimination of corpuscular antigens. This is what the so-called “professional” macrophages do.
2. Absorption, processing and presentation of antigen for T cells. These tasks are already performed by the agro-industrial complex. Such a reduction is used due to the long name of the micro-level subjects - antigen-presenting cells.

When adult formations are formed from bone marrow promonocytes, especially a lot of them fall (and linger there) into lymphocytes. Macrophages long time fulfill their functionality due to the fact that these are long-living cells in which mitochondria and a rough endoplasmic reticulum are well developed.

More about tasks

But most attention should still be paid to the fight against protozoa, viruses and bacteria that exist inside host cells. This is realized due to the presence of bactericidal mechanisms that macrophages possess. This leads to the fact that they are one of the most powerful tools of innate immunity. But that is not all. Together, they take part in the formation of the immune response in T and B lymphocytes. In addition, it is impossible not to note the role of macrophages in wound healing, elimination of cells that have already outlived their own, and the formation of atherosclerotic plaques. They literally devour harmful elements in our body. This is even indicated by their name. So, translated into Russian, “macrophage” is a “big eater”. And it should be noted that these cells are really quite large.

What are the types of macrophages?

Since the formations we are considering are tissue phagocytes, their different “modifications” can be found in different parts of the body. If we consider absolutely everything, it will take a lot of time, therefore, attention will be paid to the most significant representatives, such as:

1. Alveolar macrophages. They are located in the lungs and are engaged in cleaning the inhaled air from various harmful and polluting particles.
2. Kupffer cells. They are located in the liver. Mainly involved in the destruction of old blood cells.
3. Histocytes. They live in connective tissues, so it can be found throughout the body. But they are often called "fake" macrophages due to the fact that they are engaged in the formation of a framework for most body structures, and not directly the destruction of various harmful elements.
4. They live in the epithelium and under the mucous membranes.
5. Splenic macrophages. They are located in the sinusoidal vessels of this organ and are engaged in the capture and destruction of obsolete blood cells. No wonder the spleen is called the cemetery of dead red blood cells.
6. Peritoneal macrophages. They live in the peritoneum.
7. Macrophages lymph nodes. Where they live is obvious from the name.

Conclusion

Our body is composed. It is inhabited by many useful cells that make our life easier. Macrophages are no exception. Unfortunately, sometimes their experience is not enough for the immune system to work as necessary. And then a person gets sick. But an important advantage of our the immune system is exactly what she knows how to adapt.

Article for the contest "bio / mol / text": The immune system is a powerful multi-layer defense of our body, which is amazingly effective against viruses, bacteria, fungi and other pathogens from the outside. In addition, immunity is able to efficiently recognize and destroy transformed own cells that can degenerate into malignant tumors. However, malfunctions of the immune system (for genetic or other reasons) lead to the fact that once malignant cells take over. An overgrown tumor becomes insensitive to body attacks and not only successfully avoids destruction, but also actively “reprograms” protective cells to provide for its own needs. Having understood the mechanisms that the tumor uses to suppress the immune response, we can develop countermeasures and try to shift the balance in the direction of activating the body's own defenses to fight the disease.

This article is submitted to the contest of popular science works “bio / mol / text” -2014 in the nomination “Best Review”.

The main sponsor of the competition is the visionary company Genotek.
The competition was supported by RVC.

Tumor and immunity - a dramatic dialogue in three parts with a prologue

For a long time, it was believed that the reason for the low efficiency of the immune response in cancer is that the tumor cells are too similar to normal, healthy ones, so that the immune system configured to search for "strangers" can properly recognize them. This just explains the fact that the immune system most successfully resists tumors of a viral nature (their frequency increases sharply in people suffering from immunodeficiency). However, it later became clear that this was not the only reason.

If this article is about the immune aspects of cancer, then the work "There is no terrible claw in the world ..." You can read about the features of cancer metabolism. - Ed.

It turned out that the interaction of cancer cells with the immune system is much more versatile. The tumor does not just “hide” from attacks, it can actively suppress the local immune response and reprogram the immune cells, forcing them to serve their own malignant needs.

The “dialogue” between a degenerated, out-of-control cell with its offspring (that is, a future tumor) and the body develops in several stages, and if at the beginning the initiative is almost entirely on the side of the body’s defenses, then at the end (in the case of a disease) - goes to the side of the tumor. Several years ago, oncoimmunologists formulated the concept of “immuno-editing” ( immunoediting), which describes the main stages of this process (Fig. 1).

Figure 1. Immuno-editing (immunoediting) in the process of developing a malignant tumor.

The first stage of immuno-editing is the elimination process ( elimination) Under the influence of external carcinogenic factors or as a result of mutations, a normal cell "transforms" - acquires the ability to divide unlimitedly and not respond to regulatory signals of the body. But at the same time, as a rule, it begins to synthesize special “tumor antigens” and “danger signals” on its surface. These signals attract cells of the immune system, primarily macrophages, natural killers and T cells. In most cases, they successfully destroy “spoiled” cells, interrupting the development of the tumor. However, sometimes among these “precancerous” cells there are several in which the immunoreactivity — the ability to elicit an immune response — is weakened for some reason, they synthesize less tumor antigens, are less recognized by the immune system and, having survived the first wave of the immune response, continue to divide.

In this case, the interaction of the tumor with the body goes to the second stage, the equilibrium stage ( equilibrium) Here, the immune system can no longer completely destroy the tumor, but is still able to effectively limit its growth. In such an “equilibrium” (and not detected by conventional diagnostic methods) state of a micro-tumor can exist in the body for years. However, such hiding tumors are not static - the properties of their constituent cells gradually change under the influence of mutations and subsequent selection: an advantage among dividing tumor cells is given to those that are better able to withstand the immune system, and eventually cells appear in the tumor - immunosuppressants. They are able to not only passively avoid destruction, but also actively suppress the immune response. In fact, this is an evolutionary process in which the body involuntarily “displays” exactly the type of cancer that will kill it.

This dramatic moment marks the transition of the tumor to the third stage of development - avoidance ( escape), - on which the tumor is already insensitive to the activity of the cells of the immune system, moreover, it draws their activity to its advantage. She begins to grow and metastasize. It is such a tumor that is usually diagnosed by physicians and studied by scientists - the two previous stages proceed secretly, and our ideas about them are based mainly on the interpretation of a number of indirect data.

Dualism of the immune response and its significance in carcinogenesis

There are many scientific articles describing how the immune system fights tumor cells, but no fewer publications demonstrate that the presence of immune system cells in the immediate tumor environment is a negative factor that correlates with accelerated cancer growth and metastasis. In the framework of the concept of immuno-editing, which describes how the nature of the immune response changes as the tumor develops, this dual behavior of our defenders finally got its explanation.

We will consider some mechanisms of how this happens, using macrophages as an example. The tumor also uses similar techniques in order to deceive other cells of innate and acquired immunity.

Macrophages - “warrior cells” and “healer cells”

Macrophages are perhaps the most famous cells of innate immunity - it was from the study of their ability to phagocytosis by Mechnikov that classical cell immunology began. In mammals, macrophages are the vanguard of battle: the first to discover the enemy, they not only try to destroy it with their own forces, but also attract other cells of the immune system to the battlefield, activating them. And after the destruction of foreign agents, they are actively involved in the elimination of the damage caused, developing factors that contribute to wound healing. This dual nature of macrophage tumors is used to their advantage.

Depending on the prevailing activity, two groups of macrophages are distinguished: M1 and M2. M1 macrophages (they are also called classically activated macrophages) - “warriors” - are responsible for the destruction of foreign agents (including tumor cells), both directly and by attracting and activating other cells of the immune system (for example, T-killers ) M2 macrophages - “healers” - accelerate tissue regeneration and provide wound healing,.

The presence of a large number of M1 macrophages in the tumor inhibits its growth, and in some cases can even cause almost complete remission (destruction). And vice versa: M2 macrophages secrete molecules - growth factors that additionally stimulate the division of tumor cells, that is, they favor the development of malignant tumors. It was experimentally shown that exactly M2 cells (“healers”) usually prevail in the tumor environment. Worse than that: under the action of substances secreted by tumor cells, active M1 macrophages are “reprogrammed” into the M2 type, they cease to synthesize antitumor cytokines, such as interleukin-12 (IL12) or tumor necrosis factor (TNF), and begin to release molecules that accelerate into the environment tumor growth and germination blood vesselsthat will provide its nutrition, for example, tumor growth factor (TGFb) and vascular growth factor (VGF). They cease to attract and initiate other cells of the immune system and begin to block the local (antitumor) immune response (Fig. 2).

Figure 2. M1 and M2 macrophages: their interaction with the tumor and other cells of the immune system.

Proteins of the NF-kB family play a key role in this reprogramming. These proteins are transcription factors that control the activity of many genes necessary for M1 macrophage activation. The most important representatives of this family are p65 and p50, together forming the p65 / p50 heterodimer, which in macrophages activates many genes associated with the acute inflammatory response, such as TNF, many interleukins, chemokines and cytokines. The expression of these genes attracts more and more immune cells, "highlighting" the area of \u200b\u200binflammation for them. At the same time, another homodimer of the NF-kB family - p50 / p50 - has the opposite activity: binding to the same promoters, it blocks their expression, reducing the degree of inflammation.

Both of these activities of NF-kB transcription factors are very important, but even more important is the balance between them. It was shown that tumors purposefully secrete substances that disrupt the synthesis of p65 protein in macrophages and stimulate the accumulation of the p50 / p50 inhibitor complex. In this way (in addition to a number of others), the tumor turns aggressive M1 macrophages into involuntary accomplices of its own development: the M2 type of macrophages, perceiving the tumor as a damaged tissue site, includes a recovery program, however, the growth factors secreted by them only add resources for tumor growth. At this point, the cycle closes - a growing tumor attracts new macrophages that are reprogrammed and stimulate its growth instead of being destroyed.

Reactivation of the immune response is an important area of \u200b\u200banti-cancer therapy

Thus, in the immediate environment of the tumors there is a complex mixture of molecules: both activating and inhibiting the immune response. Prospects for the development of the tumor (and hence the prospects for the survival of the body) depend on the balance of the ingredients of this “cocktail”. If immunoactivators prevail, it means that the tumor has not completed the task and will be destroyed or its growth will be greatly inhibited. If immunosuppressive molecules predominate, this means that the tumor was able to pick up a key and will begin to progress rapidly. Understanding the mechanisms that allow tumors to suppress our immunity, we can develop countermeasures and shift the balance towards the destruction of tumors.

As experiments show, the "reprogramming" of macrophages (and other cells of the immune system) is reversible. Therefore one of promising areas Oncology immunology today is the idea of \u200b\u200b"reactivation" of the patient’s own cells of the immune system in order to enhance the effectiveness of other treatment methods. For some types of tumors (for example, melanoma), this allows for impressive results. Another example discovered by Medzhitov’s group is the usual lactate, a molecule that is produced with a lack of oxygen in fast-growing tumors due to the Warburg effect. This simple molecule stimulates the reprogramming of macrophages, causing them to support tumor growth. Lactate is transported inside macrophages through membrane channels, and potential therapy is to block these channels.

Macrophages participate in the immune response at all stages. . First, as already noted, they carry out an immediate protective reaction until an increase in the immune response, regulated by antigen-specific T cells, occurs. Secondly, they cause T-cell activation by processing and presenting the antigen to them. And finally, activated in turn by T-cells, they perform important functions in the effector mechanisms of cellular immunity, causing inflammation and destroying microorganisms, as well as tumor cells.

Cytokines enhance some macrophage functions

Circulating monocytes are able to destroy some microorganisms. When cultivated in vitro, they significantly lose this activity, but under the action of added cytokines, in particular IFA, it is restored and, in parallel, activation of additional antimicrobial mechanisms occurs, which are not normally expressed by monocytes.

Macrophage activity is a complex phenomenon. Activated phagocytic cells acquire an increased ability to destroy some microorganisms without affecting others. For example, purified JCg stimulates the bactericidal activity of human monocytes against Legionella, but it enhances growth Mycobacterium tuberculosis. This ambiguous nature of the effect is due to several reasons:

The multiplicity of effector functions performed by activated macrophages;

A wide variety of monocytes and macrophages by their properties; depending on tissue and organ, they differ in expression of MHC class II molecules and Fc receptors, the profile of secreted cytokines, and peroxidase production. Nevertheless, most researchers believe that all macrophages belong to the same cell line, and the observed differences are due to successive stages of their maturation and the influence of tissue microenvironment; in addition, the activation of certain functions may depend not only on the nature of macrophages, but also on the specific “spectrum” of cytokines and other pro-inflammatory stimuli. Presumably, macrophage activation occurs in several stages, under the influence of successive stimuli, which can serve as cytokines, endotoxin, various mediators and regulatory factors of inflammation. At each stage of activation, macrophages are capable of performing various effector functions and possess characteristic features of morphology and physiology .

In some cases, several signals are required to stimulate a specific functional activity of macrophages. For example, in order to induce the largest production of nitric oxide NO, which is toxic to bacteria and tumor cells, mouse macrophages must be stimulated first by IFA, and then TNF-A . On human macrophages, this effect is much more difficult to obtain. In most cases, this requires a series of stimuli, for example, exposure to several cytokines with simultaneous cross-linking of FceRII. Human macrophages isolated from the inflammatory focus sometimes express inducible synthase of nitric oxide, but they contain the cofactor tetrahydrobiopterin necessary for its synthesis in low concentration. Since nitric oxide performs numerous signaling functions that are not related to its toxic effect, it can be assumed that the toxicant is not this nitrogen compound itself, but mainly peroxynitrite, resulting from the interaction of N0 with oxygen reduction products. Typically, this interaction occurs only in the foci of inflammation and during the stimulation of the phagocytic activity of macrophages.

Good afternoon, dear readers!
Last time I told you about a very important group of blood cells - which are real front line fighters immune defense. But they are not the only participants in the operations to capture and destroy "enemy agents" in our body. They have assistants. And today I want to continue my story and study the functions white blood cells - agranulocytes. This group also includes lymphocytes, in the cytoplasm of which there is no granularity.
Monocyte is the most major representative white blood cells. Its cell diameter is 10-15 microns, the cytoplasm is filled with a large nucleus in the form of beans. There are few of them in the blood, only 2 - 6%. But in the bone marrow, they are formed in large numbers and mature in the same microcolonies as neutrophils. But when they enter the bloodstream, their paths diverge. Neutrophils travel in vessels and are always in readiness No. 1. And monocytes quickly settle in organs and there they turn into macrophages. Half of them go to the liver, and the rest are settled in the spleen, intestines, lungs, etc.

Macrophages - it is sedentary, completely ripe. Like neutrophils, they are capable of phagocytosis, but, in addition, they have their own sphere of influence and other specific tasks. Under a microscope, a macrophage is a very prominent cell with impressive sizes up to 40 - 50 microns in diameter. This is a real mobile factory for the synthesis of special proteins for their own needs and for neighboring cells. It turns out that macrophage per day can synthesize and secrete up to 80! various chemical compounds. You may ask: what are the active substances secreted by macrophages? It depends on where macrophages live and what functions they perform.

White blood cell function:

Let's start with the bone marrow. There are two types of macrophages involved in bone renewal — osteoclasts and osteoblasts. Osteoclasts constantly circulate through bone tissue, look for old cells and destroy them, leaving free space for future bone marrow, and osteoblasts form new tissue. Macrophages perform this work by synthesizing and secreting special stimulating proteins, enzymes and hormones. For example, they synthesize collagenase and phosphatase to destroy bone, and erythropoietin to grow red blood cells.
There are also cells - "nurse" and cells - "orderlies", which provide rapid reproduction and normal maturation of blood cells in the bone marrow. Hematopoiesis in the bones is an islet - in the middle of such a colony is a macrophage, and red cells are crowded around of different ages. Acting as a nursing mother, the macrophage supplies growing cells with nutrition - amino acids, carbohydrates, fatty acids.

A special role is played in the liver. There they are called kupffer cells. Actively working in the liver, macrophages absorb various harmful substances and particles from the intestines. Together with liver cells, they are involved in the processing of fatty acids, cholesterol and lipids. Thus, they unexpectedly are involved in the formation of cholesterol plaques on the walls of blood vessels and the occurrence of atherosclerosis.

It is not yet clear where the atherosclerotic process begins. Perhaps, an erroneous reaction to "their" lipoproteins in the blood is triggered here, and macrophages, like alert immune cells, begin to capture them. It turns out that the gluttony of macrophages has both positive and negative sides. Capturing and destroying germs is, of course, good. But the excessive absorption of fatty substances by macrophages is bad and probably leads to pathology that is dangerous to human health and life.

But to share what’s good and what’s bad for macrophages is hard, so our task is to alleviate the fate of macrophages and we take care of our own health and liver health: monitor nutrition, reduce the use of foods containing large amounts of fat and cholesterol and conduct twice a year from toxins toxins.

Now let's talk about macrophages working in the lungs.

Inhaled air and blood in the pulmonary vessels are separated by the finest boundary. You understand how important it is to ensure sterility of the airways under these conditions! That's right, here this function is also performed by macrophages that wander around the connective tissue of the lungs.
They are always filled with the remains of dead lung cells and microbes inhaled from the surrounding air. Macrophages of the lungs multiply immediately in the area of \u200b\u200btheir activity, and their number increases sharply in chronic diseases of the respiratory tract.

For smokers! Dust particles and tarry substances of tobacco smoke strongly irritate the upper respiratory ways, damage the mucous cells of the bronchi and alveoli. Pulmonary macrophages, of course, capture and neutralize these harmful chemical products. Smokers sharply increase activity, the number and even the size of macrophages. But after 15 - 20 years, the limit of their reliability is depleted. The delicate cellular barriers separating air and blood are broken, the infection breaks into the depths lung tissue and inflammation begins. Macrophages are no longer able to fully function as microbial filters and give way to granulocytes. So, long-term smoking leads to chronic bronchitis and a decrease in the respiratory surface of the lungs. Excessively active macrophages corrode the elastic fibers of the lung tissue, which leads to difficulty breathing and hypoxia.

The saddest thing is that when working on wear, macrophages cease to perform very important functions - this is the ability to fight cancer cells. Therefore, chronic hepatitis is fraught with the development of liver tumors, and chronic pneumonia - lung cancer.

Macrophages spleen.

In the spleen, macrophages perform the function of “killers”, destroying aging red blood cells. Traitorous proteins, which are a signal for elimination, are exposed on the membranes of red blood cells. By the way, the destruction of old red blood cells occurs both in the liver and in the bone marrow itself - wherever there are macrophages. In the spleen, this process is most evident.

Thus, macrophages are great workers and the most important orderlies of our body, while performing several key roles at once:

1. participation in phagocytosis,
2. preservation and recycling of important nutrients for the needs of the body,
3. isolation of several tens of proteins and other biologically active substancesregulating the growth of blood cells and other tissues.

Well, we know functions of leukocytes - monocytes and macrophages. And again, there was no time left for lymphocytes. We will talk about them, the smallest defenders of our body next time.
In the meantime, let's improve our health and strengthen our immunity by listening to Mozart's healing music - Heart Symphony:

I wish you good health and prosperity!