22 March 2010

Microchimerism: alien cells among their own

Strangers
The body of each of us contains cells carrying foreign DNA. They are capable of both crippling and healingAlla Astakhova, the magazine "Results", 22.03.2010

These searches for excitement are comparable to a real hunt for researchers. It seems that we are lucky now. The procedure is not pleasant, but it was necessary to take a small scraping of tissues from the examined man. Ready! In the eyepieces of the microscope, you can see how among the host of cells, each of which glows with red-green fluorescent dots (they mark the male pair of X chromosomes), a strange red pair – XX suddenly flashes. A female cell in a man's body? From where? There is an explanation: when our subject was still in the womb, a particle of his mother entered his body through the placenta. We found the descendants of that very cell during the experiment. It also contains maternal DNA. An incredible thing? Not at all – scientists find maternal cells in 20 percent of the examined. However, there are probably even more carriers of cells with a foreign genome in the human population. After all, the fetus is able to "share" its cells with the mother through the same placenta. Fraternal twins, while in the womb, also exchange cells. Through the mother's body, we can receive the cells of older brothers and sisters who were in it before us, or almost the cells of grandmothers...

Analyzing all these cases, scientists remember the Chimera for a reason – a mythological monster that combined parts of the bodies of different animals: a lion, a snake and a goat. After all, many people, if not all of us, may turn out to be chimeras as a result. However, there are probably very few foreign cells in our body – according to estimates, about one in a million. Therefore, researchers have come up with a special name for the phenomenon – microchimerism. Recently, it has become the object of close attention of doctors. It turned out that these tiny particles of someone else's life, which have taken root in our body at the whim of nature, are capable of carrying both diseases and healing from them.

Without barriersEven 60 years ago, scientists first found out that the mother's cells can enter the baby's body through the placenta.

Why were maternal cells first found in boys? In the body of a girl, all of whose native cells have a set of XX chromosomes, maternal cells with the same set are simply impossible to notice. At first, this discovery did not please anyone. Doctors were scared, for example, that female cells of their mothers were found in cancerous tumors in young boys. Were they not the "trigger" of a terrible disease? "Most likely, they could have ended up in tumors in accordance with the principle of "where it's thin, it breaks there," says Sergey Kiselyov, head of the Laboratory of Genetic Foundations of Cellular Technologies at the N. I. Vavilov Institute of General Genetics of the Russian Academy of Sciences. – Usually the body rejects someone else's genetic material, however, immune breakdowns associated with cancer are capable of change the picture."

However, in those years, no one understood the essence of the phenomenon yet. Moreover, there were types of cancer that were often diagnosed in the mother and newborn at the same time. In the 50s and 60s, they even tried to come up with a kind of vaccine from the "contagious" cells of the mother carrying cancer - they injected pregnant women with their husbands' cells, hoping to instill immunity from the tumor in the unborn child.

After a few years, it became clear that the fears were greatly exaggerated. Maternal cells began to be found in newborns not only in tumors. And in the late 70s, scientists proved the existence of reverse cell traffic - from the child to the mother. At that time, an article by American scientists who found cells with the Y chromosome in the blood of a woman pregnant with twins of boys made a sensation. And yet, at first, researchers were in no hurry to draw far–reaching conclusions - it was believed that this phenomenon could only be found in newborns, because immunity simply would not allow strangers to stay in a healthy person's body for a long time. The fact that maternal cells were found at a more mature age in children suffering from serious forms of immunodeficiency seemed to only confirm the rule.

Everything changed in the 90s, when Jay Lee Nelson, an employee of the Fred Hutchinson Cancer Research Center in Seattle and one of the largest experts on the problem of microchimerism, managed to find preserved XX cells in healthy adults, and one of them was 46 years old by that time. The cells of the child in the mother's body, as it turned out, could also demonstrate amazing vitality. For example, one woman's Y chromosome was found in her blood several decades after she gave birth to sons. How could cells exist in the body for so long? After all, most of them have a limited life span. "The exception is stem cells, which can divide endlessly and give rise to a variety of specialized species, from immune system cells to those that make up tissues and organs," says Lee Nelson. Scientists have suggested that the "long–lived" alien cells that can be found in the body are most likely descendants of stem cells that once got into it. Further experiments only strengthened them in this idea. It became clear that most of us, without knowing it, can live life as microchimers – foreign cells are with us for a long time, maybe forever.

Regulate itNew research by scientists has added fuel to the fire, suggesting the following: if foreign cells enter the human body, it is necessary for some reason.

Baruch Rinkevich, a senior researcher at the National Institute of Oceanography in Tel Aviv, suggested that microchimerism is simply necessary - it allows you to train and train the immune system. It is important to take into account that the primary and main function of immunity is not protection from infections at all, as it has long been believed. At one time, Nobel laureate Ilya Mechnikov, who expressed the idea that the immune system is designed not so much to repel microbial invasions as to regulate the processes taking place in the body, was criticized by both Robert Koch and Paul Ehrlich. It took a whole century for the attitude to the issue to change. "The problem is that even healthy people quite often have somatic cell mutations," says Baruch Rinkevich. – If the body does not know how to control the reproduction of such somatic variants, they will actually parasitize it. It is reasonable to assume that a variety of cellular mechanisms are needed in order to cope with this threat. Microchimerism that occurs during pregnancy is a byproduct of teaching the developing embryo various mechanisms to prevent the spread of dangerous mutations. To do this, the mother–child interface must always be active in both directions, and the sooner this starts happening, the better. Moreover, various components of the mother's immune system must also be systematically activated." A good way to activate the immune system is the mutual exchange of cells between mother and child.

It is this "cellular interface", according to the researchers, that forms such a useful thing as innate immunity. "It is well known that immune cells penetrate through the placenta from mother to child, including the so–called memory leukocytes that can live in the body for a long time," says Alexander Poletaev, a leading researcher at the P. K. Anokhin Research Institute of Normal Physiology of the Russian Academy of Medical Sciences. "It is precisely with this phenomenon that the child's "inheritance" of the mother's immune status, which was present during pregnancy, is connected." Simply put, we are already at birth immune to the same diseases as our mothers, although the child's body has not yet met with their pathogens. It's just that our immune system learned and trained with the help of maternal immune cells. Researchers are aware of real "immunological sagas" when resistance to certain infections is transmitted through offspring in several generations.

However, there are cases when the opposite happens – the mother's immunity, which for various reasons has given way, receives unexpected support from the immune cells of the child. 70 years ago, the American Nobel laureate Philip Hench observed amazing situations when women suffering from an incurable autoimmune disease, rheumatoid arthritis, practically recovered during pregnancy. But, however, after a few years, the disease still returned to them. At first, doctors considered a change in hormonal status to be the cause of what was happening. However, Jay Lee Nelson and colleagues discovered immune "helpers" coming from the child – leukocyte antigens. The more they differed in the embryo and the mother, the more likely it was to temporarily get rid of the disease. At a high price

And yet nature would not be itself if it did not assign a ruinous fee for "immunity lessons". Immune cells produce special molecules, antibodies involved in the "cleaning" of cellular "garbage". "Imagine a situation: a woman has diseased kidneys or thyroid gland. Pathogenic processes are most often associated with increased cell death, while each organ has its own "garbage", – says Alexander Poletaev. – The patient, accordingly, produces a significant amount of antibodies to "clean" these cells. Her baby's kidneys are healthy. But the immune system is still trained to produce more and more "scavengers". The result may be inflammation. Someone will say – genetics, inherited from the mother. But it's not like that." Scientists have yet to study this mechanism and possibly find a remedy for autoimmune diseases in which the body attacks its own cells. After all, having understood how he learns to do this, you can retrain him.

Another example of the body's violent attacks on cells is associated with lupus of newborns – an autoimmune disease often found in children whose mothers were sick with systemic lupus erythematosus. Scientists decided to study this connection in the hope of finding traces of the destructive work of maternal antibodies transmitted to the child. However, the startling truth was revealed when they examined the myocardial tissue of such children who died of a heart attack. We studied the hearts of boys again and found a huge number of female XX cells in them. "These observations indicate that the immune attacks of the body in newborn lupus are directed against the descendants of maternal cells located in the heart of the embryo," says Jay Lee Nelson. "It is possible that some other autoimmune diseases may be associated with the fact that the body attacks not its own, as is commonly thought, but foreign cells embedded in its tissues."

Scientists intend to seriously address this hypothesis. Many facts speak in her favor. For example, women are more likely to suffer from autoimmune diseases. Moreover, these diseases usually strike after the age of 40 – just when many have gone through pregnancy and the descendants of their own children's stem cells are present in the body. Getting close to this topic, scientists have already studied patients suffering from scleroderma, an autoimmune disease whose symptoms are known to surgeons: they surprisingly resemble complications after transplantation. And again, the mothers of boys came into the field of view of scientists. Comparison with the control group showed that they have more male XY cells than the rest of the women.

But if this is so, is it not too expensive for women to pay into the piggy bank of nature for motherhood? Experts are sure: you have to pay in hard cash. However, in the relationship between the child and the mother, even at the cellular level, there is no nobility. For example, scientists know the rejuvenating effect of stem cells transmitted from the embryo to the mother during pregnancy. "It can manifest itself for several years after childbirth," says Alexander Poletaev. And maternal stem cells, in turn, are able to "treat" the embryo: in boys with type I diabetes, which affects the cells that produce insulin, female cells were found in the pancreas, selflessly coming to the rescue.

But the main thing that scientists have yet to prove is that perhaps the mother's cells are responsible not only for immunity. They are able to penetrate the brain structures. "Do they affect brain development?" asks Jay Lee Nelson. It seems that in this case, the mother and child will be able to tell each other with confidence: "You are me"

Portal "Eternal youth" http://vechnayamolodost.ru22.03.2010

Found a typo? Select it and press ctrl + enter Print version