2022-06-16 20:09:34
One of the most fascinating facts in biology is the presence of genes and proteins that function only during fetal life and are replaced by “adult” versions of those same genes after birth. We have a paradigmatic example of this phenomenon in the genes of hemoglobin, as we know the protein in red blood cells that transports oxygen to the organs. Fetal hemoglobin, which the fetus uses to oxygenate its organs, is not the same as adult hemoglobin: for its manufacture it needs a gene that only works during life in the maternal womb. The most important characteristic of this type of hemoglobin is that it has a greater oxygen uptake force than adult hemoglobin. The greater strength with which fetal hemoglobin binds oxygen allows the fetus to “rob” maternal hemoglobin of some of its bound oxygen. We can say that fetal hemoglobin “pulls” oxygen more strongly than adult hemoglobin and this allows it to remove it from the latter to oxygenate itself in the placenta and transport oxygen to the entire organism of the growing fetus.
If the role played by fetal hemoglobin has been sufficiently elucidated, this is not the case with all fetal proteins that are replaced after birth by their corresponding adult versions. One of the most studied fetal proteins, but about which, however, all the secrets are not yet known, is the so-called alpha-fetoprotein, and I want to talk about it today. The main reason that explains my interest in this protein is that I did my doctoral thesis on it, back in the 80s of the last century. Heavens! How bad those words sound when I hear them out loud!
In those distant, but happier, years of my career, when I still did not know what was waiting for me and worked with an enthusiasm inappropriate for a rational being, I dedicated great efforts to the Institute for Scientific Research on cancer -located in the commune of Villejuif, on the outskirts of Paris–, to try to understand what the function of this protein was during pregnancy. Our thinking was that alpha-fetoprotein, a blood protein produced mainly by the liver of the fetus, was the main transporter of polyunsaturated fatty acids, particularly omega-3 fatty acids, to the developing brain. If we rule out water, the brain contains 60% fat, a large percentage of which is polyunsaturated, which is essential to maintain the fluidity of the neuronal membranes that transmit nerve impulses. The efficient transport of omega-3 fatty acids to the organ that most needs them for proper development during fetal life could not be carried out efficiently enough by albumin. This is the adult version of alpha-fetoprotein, and it preferentially carries saturated fatty acids, such as those found in shortening and butter. The situation was therefore, at least on paper, very similar to that of fetal and adult hemoglobins, with alpha-fetoprotein and albumin each performing their function most effectively at different times in life.
Alpha-fetoprotein is also produced in high amounts by certain liver tumors, which places it in the category of so-called oncofetal proteins, that is, proteins produced in fetal life that disappear after birth, but can reappear. occur in the case of the development of certain types of tumors (hence the prefix onco, shared by the word oncology, to refer to them). Alpha-fetoprotein levels in adult blood may therefore be indicative of the presence of a liver tumor. In addition, abnormal levels of alpha-fetoprotein in maternal blood may also indicate Down syndrome or other abnormalities that impact the development of the fetal nervous system.
Few, however, in those years at the end of the last century, studied other possible functions of alpha-fetoprotein, related not so much to the supply of essential nutrients to the developing brain, but to the modulation of the immune response. Indeed, the polyunsaturated fatty acids transported by alpha-fetoprotein may be precursors of molecules with potent modulating activity of immune activity, such as the so-called prostaglandins.
Studies soon began to appear indicating a role for alpha-fetoprotein as an inhibitor of antibody production or lymphocyte proliferation. Recently, it has been published that alpha-fetoprotein can inhibit the activity of cells called natural killer (NK) or natural killers. These cells are very important in the fight against tumors and against viral infections in adult life. Inhibition of NK cells can be effected by the direct action of alpha-fetoprotein on them, or by its action on antigen-presenting cells, the so-called dendritic cells, which, in the presence of alpha-fetoprotein, decrease the production of factors NK cell stimulators.
Other studies suggest that, in addition to the above effects, alpha-fetoprotein can enhance the production of so-called regulatory T lymphocytes, whose function is more related to tolerance towards our own cells than to the fight against microorganisms. This function may be related to an anti-inflammatory activity of alpha-fetoprotein.
Previous and very recent studies suggest that alpha-fetoprotein plays an important role in preventing the mother’s immune system from attacking and rejecting the fetus, which, after all, is just a foreign organism growing in inside the maternal body. If this is confirmed, the fetus itself would stimulate the mother’s tolerance by producing high amounts of alpha-fetoprotein during its development. This would also be consistent with the fact that the production of alpha-fetoprotein by certain tumors could help them escape the activity of the immune system to control them.
Additional studies are needed to detail the functions of alpha-fetoprotein as a modulator of the immune system. Understanding the mechanisms of action of this protein in relation to the diversity of molecules that it can have attached could open new avenues for the treatment of tumors through the potentiation of immunotherapy, with treatments that block its inhibitory activity, or also new strategies for the treatment of autoimmune diseases, enhancing, in this case, the immunosuppressive activity of this protein.
Although the past of alpha-fetoprotein is already remote, as I said above with a certain air of nostalgia, a promising future still opens up, leading to understanding the importance of all the various functions of this fascinating protein.
Referencia: Paul V. Munson, Juraj Adamik, Lisa H. Butterfield. Immunomodulatory impact of α-fetoprotein. Open Access. Published: May 09, 2022 DOI: https://doi.org/10.1016/j.it.2022.04.001
Jorge Laborda (06/17/2022)
Works by Jorge Laborda.
Your defenses against coronavirus
Your defenses against coronavirus
Deflamed immunology: An introduction to the immune system and its pathologies
Deflamed immunology: An introduction to the immune system and its pathologies
Deflamed immunology: An introduction to the immune system and its pathologies
Kilo of Science Volume XII eBook
Kilo of Science Volume XII Paper
Kilo of Science Volume I. Jorge Laborda
Kilo of Science Volume II. Jorge Laborda
Kilo of Science Volume III. Jorge Laborda
Kilo of Science Volume IV. Jorge Laborda
Kilo of Science Volume V. Jorge Laborda
Kilo of Science Volume VI. Jorge Laborda
Kilo of Science Volume VII. Jorge Laborda
Kilo of Science Volume VIII. Jorge Laborda
Kilo of Science Volume IX. Jorge Laborda
Kilo of Science Volume X. Jorge Laborda
Kilo of Science Volume XI. Jorge Laborda
Matrix of homeopathy
Chained circumstances. Ed.Lulu
Chained circumstances. Amazon
One moon, one civilization. Why the Moon tells us that we are alone in the Universe
One moon, one civilization. Why the Moon tells us that we are alone in the Universe
One Moon one civilization why the Moon tells us we are alone in the universe
The thousand and one bases of ADN and other science stories
Adenius Fidelius
The intelligence funnel and other essays
The gods have been cloned
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