Angiotensin-converting enzyme increases blood pressure and antitumor immunity
Scientists at Emory University (Georgia), working under the guidance of Professor Kenneth Bernstein, created genetically modified mice whose immune system more effectively suppressed the growth of implanted tumors due to enhanced synthesis of angiotensin-converting enzyme by macrophages.
The enzyme cleaves small fragments from tumor proteins that are recognized by the immune system, which, upon learning about the presence of a tumor in the body, triggers a complex of antitumor immune reactions. Angiotensin-converting enzyme plays a key role in the regulation of blood pressure and is the target of traditional antihypertensive drugs. Its main function is to convert an inactive form of the hormone angiotensin into an active one by chemically cleaving two amino acids from one of the ends of its molecule. Angiotensin narrows blood vessels, increases the feeling of thirst and indirectly increases the retention of sodium by the kidneys, so suppressing the production of its active form reduces blood pressure.
However, angiotensin is not the only target of the angiotensin-converting enzyme. In an earlier work, the authors found that a change in the activity of this enzyme affects a number of processes, including the ability to conceive and the formation of red blood cells in the bone marrow.
To clarify the role of angiotensin-converting enzyme in the functioning of the immune system, scientists have created genetically modified mice in whose body the activity of the gene of this enzyme was observed exclusively in macrophages.
Macrophages perform the function of digesting foreign proteins (antigens) and presenting them on their surface to T-lymphocytes. As a result, T-lymphocytes begin to proliferate and destroy infected cells containing antigens with which they were previously introduced by macrophages. Most often, the targets of T-lymphocytes are cells infected with viruses, but sometimes they can also be tumor cells.
The introduction of genetically modified mice with cells of several types of melanoma and lymphoma led to the development of tumors, but their size was significantly smaller than in normal animals of the control group. In addition, the tumors of the modified animals contained more tumor-specific lymphocytes.
The authors warn that in a normal state macrophages practically do not produce angiotensin-converting enzyme, therefore the effect described by them should be considered as artificial. They also note that millions of people with high blood pressure take angiotensin converting enzyme inhibitors, such as enalapril and lisinopril, and do not suffer from immunodeficiency.
At the same time, there is evidence that cells similar to macrophages synthesize angiotensin-converting enzyme in response to the ingestion of pathogens such as pathogens of sarcoidosis and leprosy.
The authors believe that their discovery points to a promising strategy for improving the effectiveness of the functioning of the human immune system. As one of the options, doctors will be able to isolate macrophages from the patient's blood, modify their ability to synthesize angiotensin-converting enzyme and inject it back to the patient.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
11.04.2008