Myelopeptide-2 (MP-2)

Myelopeptide-2 recovers interleukin-2 synthesis and interleukin-2 receptor expression in human T lymphocytes depressed by tumor products or measles virus

Myelopeptide-2 (MP-2; Leu-Val-Val-Tyr-Pro-Trp), originally isolated from the supernatant of porcine bone marrow cell culture, is able to restore the mitogen responsiveness of human T lymphocytes inhibited by conditioned medium from HL-60 leukemia cells or measles virus. This effect is based on the ability of MP-2 to recover the reduced interleukin (IL)-2 synthesis and IL-2 receptor (IL-2R) expression in human T lymphocytes treated with these harmful agents. The involvement of other cytokines in MP-2 restoration of the reduced IL-2 synthesis in T lymphocytes is experimentally studied. It is shown that T helper (TH) 1 and TH2 cytokines are acting in close interaction, the character of which depends on the immune status of the T-lymphocyte donors. The data obtained allow one to suggest that the MP-2 involvement in regulatory processes is directed to the maintenance of immune homeostasis. This peptide is perspective to be applied in antitumor and antivirus therapy.

[Synthesis and properties of the retro-analogue of myelopeptide MP-2]

The bone marrow myelopeptide MP-2 (Leu-Val-Val-Tyr-Pro-Trp), exhibiting antitumor activity, and its retro-analogue (Trp-Pro-Tyr-Val-Val-Leu) were synthesized, and their properties were studied. The in vitro and in vivo activities of retro-MP-2 were comparable with those of MP-2. Both peptides equally restored the functional activity of T-lymphocytes inhibited by toxins released by HL-60 cells and inhibited by 70-82% the growth of various types of transplantable solid tumors: Ca-755 adenocarcinoma of the mammary gland, Lewis adenocarcinoma of the lung, and S180 sarcoma. The positions and intensities of the Cotton effects in CD spectra of the MP-2 peptide and its retro-analogue in various solvents are almost indistinguishable. The positions of extrema and integral intensities of the amide I and amide A bands in IR spectra of both peptides were practically identical. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 3; see also http://www.maik.ru.

The bone marrow peptide (myelopeptide-2) abolishes induced by human leukemia HL-60 cell suppression of T lymphocytes

Myelopeptide-2 (MP-2) Leu-Val-Val-Tyr-Pro-Trp originally isolated from the supernatant of porcine bone marrow cell culture was examined for its capacity to restore the mitogen responsiveness of human T lymphocytes inhibited by conditioned media from HL-60 leukemia cells (HL-60 CM). MP-2 added to phytohemagglutinin (PHA)-stimulated T lymphocytes together with HL-60 CM abolished the suppression of T-lymphocyte proliferative response in a dose-dependent manner. Another bone marrow hexapeptide Phe-Leu-Gly-Phe-Pro-Thr, MP-1, did not display this action in that experimental system. MP-2 was also effective being added after T-lymphocyte exposure to HL-60 CM which suggests its recovery but not protective effect on T-lymphocytes treated with tumor cell products. Flow cytometry analysis revealed HL-60 CM influence on the expression of CD3 and CD4 T-cell surface antigens. It decreased the content of CD3- and CD4-positive cells and induced the appearance of T lymphocytes with reduced density of CD3 and CD4 antigens. MP-2 was able to restore the T-cell phenotype altered by HL-60 CM. MP-2 seems to be promising in anti-tumor therapy.

Myelopeptides: new immunoregulatory peptides

Bone marrow cells of various animal species and humans produce a group of bioregulatory peptides called myelopeptides (MPs). MPs have been isolated and purified, and their physico-chemical properties have been investigated. MPs have a wide spectrum of functional activities: immunoregulatory, differentiating, and opiate-like. A new immunocorrective drug, Myelopidum, which is used effectively in clinical practice for treating diseases accompanied by immunodeficiency, has been created on the basis of MPs. Administration of Myelopidum after surgery prevents 50% to 70% of postsurgical complications, particularly postsurgery pneumonia, and also normalizes the number and balance of T-helper cells, T-suppressor cells, and B-lymphocytes in patients with chronic pulmonary diseases, resulting in a beneficial clinical effect, including a significant prolongation of remission periods. Myelopidum is also used in veterinary medicine for prophylaxis and treatment of pneumonia and enteritis in newborn and young animals. The primary structure of several myelopeptides is established. The functional activities of two, MP-1 (Phe-Leu-Gly-Phe-Pro-Thr) and MP-2 (Leu-Val-Val-Tyr-Pro-Trp), are being investigated.

Myelopeptides: bone marrow regulatory mediators

Bone marrow cells of various animal species and men produce a group of bioregulatory peptides called myelopeptides (MPs). A highly purified MP fraction and some individual molecules have been isolated from the supernatant of porcine bone marrow cell cultures by reverse phase chromatography. MPs have a wide spectrum of functional activities: immunoregulatory, differentiating and opiate-like. They evoke 2.5-fold stimulation of antibody production to various antigens. They correct some immune defects in MRL/lpr mice with spontaneous autoimmune disorders that results in 2-fold prolongation of the life span of these mice. MPs influence the differentiation of bone marrow and peripheral blood cells derived from healthy and leukemic donors. They induce terminal differentiation in the leukemic human HL-60 cell line. MPs also show an effect on pain sensitivity. A new immunocorrective drug Myelopid has been developed on the basis of MP mixtures. This drug is effectively used in Russia both in medicine and veterinary practice for prophylaxis and treatment of diseases accompanied by immunodeficiency. Two individual MPs were isolated and identified: Phe-Leu-Gly-Phe-Pro-Thr (MP-1) and Leu-Val-Val-Tyr-Pro-Trp (MP-2). MP-1 displays immunoregulatory activity; MP-2 abolishes the inhibitory effect of leukemic cells on T-lymphocyte functional activity. MPs seem to provide not only immunoregulation but also to participate in complex interactions between different systems in the organism.