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Biomedical subjects

A A Mikhailova

Publications and source records attributed to A A Mikhailova.

At least 19 recordsLinked to original sources
PubMed2005

Induction of differentiation in leukemic cell strains with myelopeptide-4.

We studied the capacity of myelopeptide-4 (regulatory peptide of the bone marrow origin) to induce terminal differentiation of HL-60 and K-562 leukemic cells. Myelopeptide-4 increased the expression of CD14 and CD38 differentiation antigens on the surface of HL-60 cells and of CD44 antigen on K-562 cells, induced the appearance of mature monocyte/macrophages in HL-60 culture and hemoglobin-producing cells in K-562 cell culture, and stimulated phagocytic activity of THP-1 leukemic cells. Myelopeptide-4 is an endogenous factor of cell differentiation, a prospective agent for antileukemic therapy.

ADP-ribosyl Cyclase 1↗
PubMed2002

Effect of myelopeptide-2 on the development of spontaneous and urethane-induced tumors in mice.

We studied the effect of endogenous immunoregulatory myelopeptide-2 on the development of spontaneous and urethane-induced lung adenomas. Long-term treatment with myelopeptide-2 (25 injections) in parallel with urethane poisoning decreased animal mortality caused by this carcinogen. Short-term treatment with myelopeptide-2 decreased the number of spontaneous and urethane-induced lung tumors in mice. Myelopeptide-2 delayed the appearance of urethane-induced tumors irrespective of the number of injections.

Adenoma↗
PubMed2002

Multiple anchoring of myelopeptides on sequential oligopeptide carriers (SOC(n)): synthesis, conformation and studies in human leukemia cells.

Myelopeptides, MP-6 (Val-Asp-Pro-Pro) and MP-4 (Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro), induce metabolic changes in human leukemia cells, HL-60, characteristic of the differentiation process, which should be regarded as a promising therapeutic approach in cancer and related diseases. With the aim to optimize the differentiation effect of MPs, they were coupled to the Lys-N(epsilon)H(2) groups of a sequential oligopeptide carrier Ac-(Lys-Aib-Gly)(4), SOC(4), and the constructs obtained were studied. The rigid 3(10) secondary structure of the carrier is preserved even after linkage of the MPs, which also maintain their initial conformations without interacting either with each other or with the carrier, as demonstrated by (1)H nuclear magnetic resonance (NMR) spectroscopy. It is concluded that the carrier accommodates the presentation of MPs, thus improving their differentiation effect on human leukemia cells.

Amino Acid Sequence↗
PubMed2000

A new endogenous differentiating factor (myelopeptide-4) for myeloid cells.

Along with known lymphokines involved in the regulation of hematopoiesis, a new differentiating factor (myelopeptide-4, MP-4) for myeloid cells was found. The peptide (Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro) originally isolated from the culture medium of porcine bone marrow cell culture was examined for its ability to induce differentiation in two human myeloid leukemia cell lines, HL-60 and K-562. Agents with well-known differentiation-inducing activity, such as phorbol myristate acetate, dimethylsulfoxide and the lymphokines were used as a reference. It has been shown that MP-4 significantly influences the integral characteristics of metabolism, expression of surface antigens and morphology of these cells. It decreased the level of chromosomal DNA synthesis and, in parallel, increased the total protein synthesis in both HL-60 and K-562 cells. MP-4 induced the expression of CD14 monocyte-specific surface antigen and the appearance of mature monocytes/macrophages in HL-60 cell cultures. There was a good correlation of cell metabolic/morphological changes and the CD14 marker expression for HL-60 cells. A similar phenomenon was observed in K-562 cells treated with MP-4 when the levels of hemoglobin synthesis were detected in their cytoplasm. Thus, we consider MP-4 as a new endogenous differentiating factor for myeloid cells.

Amino Acid Sequence↗
PubMed1997

Bone marrow immunoregulatory peptides (myelopeptides): isolation, structure, and functional activity.

Myelopeptides (MPs) are bioregulatory mediators of bone marrow origin. Several individual MPs have been isolated from the supernatant of porcine bone marrow cell culture by successive solid phase extraction and reversed-phase high performance liquid chromatography. Two of them, MP-1 (Phe-Leu-Gly-Phe-Pro-Thr) and MP-2 (Leu-Val-Val-Tyr-Pro-Trp), were synthesized and their biological activities were comprehensively studied. Both hexapeptides display pronounced immunoregulatory activity but their final effects as well as mechanisms of action are different. Peptides MP-1 and MP-2 are identical to conservative fragments 33-38 alpha- and 31-36 beta-chains of hemoglobin, respectively. The sequences of other isolated MPs have no homology with any functional protein. The role of MPs in bioregulatory processes in vivo is discussed.

Adjuvants, Immunologic↗
PubMed1996

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.

Bone Marrow↗
PubMed1995

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.

Activins↗
PubMed1995

Immunoregulatory effects of two bone-marrow hexapeptides (myelopeptides) in experimental models of immunodeficiency.

Myelopeptide 1 (MP-1, Phe-Leu-Gly-Phe-Pro-Thr) and myelopeptide 2 (MP-2, Leu-Val-Val-Tyr-Pro-Trp) are hexapeptides originally isolated from porcine bone-marrow cell culture. MP-1 enhanced the number of antibody-forming cells in NZB mouse spleen cells in vitro and increased the antibody production in Cy-treated (CBAxC57B1/6)F1 mice in vivo. MP-1 increased ConA-induced proliferation of both NZB spleen cells in vitro and spleen cells of Cy-treated mice in vivo. MP-1 restored polyclonal IgG synthesis depressed by PWM in the NZB spleen cell culture. MP-2 also evoked immunoregulatory effects which were less pronounced and realized at higher concentrations than effects of MP-1. Neither MP-1 nor MP-2 affected LPS-induced spleen cell proliferation in both NZB- and Cy-treated (CBAxC57B1/6)F1 mice.

Adjuvants, Immunologic↗
PubMed1994

Myelopeptide-1 blocks the T-suppressor activity.

The immunoregulatory properties of two myelopeptides (MPs) [Phe-Leu-Gly-Phe-Pro-Thr (MP-1) and Leu-Val-Val-Tyr-Pro-Trp (MP-2)] were studied. The antibody production-stimulating activity was determined in the culture of lymph node cells (LNC) obtained from mice on the 4th day of the secondary immune response to sheep red blood cells (SRBC). T suppressors were induced in mouse spleen cell (SC) culture by incubation with concanavalin A (Con A) for 48 h. Immune LNC were cultured alone or with T suppressors in the presence or absence of MPs. After cultivation, the immune response was estimated by enumeration of indirect antibody forming cells (AFC). MP-1, but not MP-2, increased the number of AFC and abolished Con A induction of T suppressors in SC suspensions. MP-1 also fully blocked and MP-2 only partly decreased the inhibitory effect of T suppressors in the culture of immune LNC. Immunoregulatory peptide MP-1 may participate in regulation of the antibody response and in development of some states of immunological tolerance.

Amino Acid Sequence↗
PubMed1993

Purification and properties of a 155 kDa bone marrow-derived glycoprotein enhancing the activity of granulocyte-macrophage colony stimulating factor (GM-CSF).

A protein has been purified from pig bone marrow which enhances the activity of exogenously added granulocyte-macrophage colony stimulating factor (GM-CSF) on mouse myelopoietic colony formation in vitro. The substance alone did not exhibit any colony stimulating activity. The active fraction was isolated from the medium of pig bone marrow suspension cultures during 20-24 h. Purification to homogeneity was then performed by subsequent HPLC and SDS-PAGE. The GM-CSF enhancing protein was identified as a 155 kDa glycoprotein.

Animals↗
PubMed1991

Myelopeptides effect on longevity and immunological parameters in mice with congenital immunodeficiency.

Myelopeptides (MP) are regulatory molecules produced by animal and human bone marrow cells. A highly purified MP fraction has been isolated from supernatant of the porcine bone marrow cell culture by gel chromatography on Sephadex G-25 and HPLC. MP correct defective antibody response to SRBC in MRL/lpr mice with spontaneous autoimmune disease and increase hemoglobin level in Wv/Wv mice with congenital anemia. Hemoglobin enhancement in Wv/Wv mice is connected with MP influence of differentiation and proliferation of hemopoietic stem cells. MP correction of immunological parameters in MRL/lpr mice resulted in 2-fold prolongation of their life span.

Adjuvants, Immunologic↗
PubMed1987

The effect of bone marrow regulatory peptides on antibody production by hybridoma cells.

Peptides produced by bone marrow cells (myelopeptides) increase antibody production. Since antibody producing cells seemed to be their targets, we tested in these experiments the effect of myelopeptides on antibody production by 2B2 and 2C12 hybridoma cells. Both hybridomas produce anti-SRBC monoclonal antibodies of the IgM class. The 2B2 cells do not produce direct haemolytic plaques and less than 5% of them produce the indirect ones during the 90-min assay period. When they were cultivated with myelopeptides for 15 h, the number of indirect plaques increased two-fold. A slightly lower increase was observed after 24 h of incubation, while the 48-h incubation period did not increase the number of detected plaques. After 6 h of preincubation, only a slight increase in indirect plaque numbers was observed. About 25% of the 2C12 hybridoma cells produce both direct and indirect haemolytic plaques during the assay period. The effect of myelopeptides was studied only on the indirect ones and no clear effect was observed. Only after the 15-h incubation period a slight increase in plaque numbers was observed. Because the myelopeptides affect antibody production of hybridoma cells, antibody producing cells are evidently the targets of these substances. It remains to be established, whether they are the only target cells in the myelopeptide action on the immune response.

Animals↗
PubMed1986

Myelopeptides--bone marrow mediators with immunostimulating and endorphin-like activity.

Bone marrow cells produce soluble mediators with structural and functional heterogeneity. They were found to stimulate antibody production at the peak of the immune response, owing to compounds of a peptide nature (Mr 2000-1300). Active material was isolated by means of gel chromatography and electrophoresis. This material positively reacts with ninhydrin, and has maximum absorption close to 278 nm. Its antibody-stimulating activity decreased or stopped completely after treatment with proteolytic enzymes. Apart from the immunostimulating activity, bone marrow mediators have opiate-like activity. They have an analgetic effect, and interact with the opiate receptors of brain nerve cells. After a physicochemical and functional analysis, we conclude that bone marrow produces regulatory peptides that were previously unknown. We called them myelopeptides.

Analgesics↗
PubMed1981

Antibody production stimulating activity of bone marrow cells from tolerant rats.

The antibody production stimulating activity of BM cells from SRBC-tolerant and normal rats were studied. Tolerance was induced by repeated injections of SRBC which were begun within 24 h after birth. BM cells obtained from tolerant animals 14-24 days after the last SRBC injection or from normal rats of the same age were used. LN cells from mice immunized with SRBC or BRBC served for the detection of BM activity. Four days after the second injection of antigen, LN cells were removed and cultivated alone or with BM cells from tolerant or control rats for 16 h. After cultivation, immune reaction was estimated by enumeration of indirect PFC. BM cells from SRBC-tolerant rats increased the number of SRBC PFC in the culture more than BM cells from control rats. On the other hand, the stimulatory activity of the BM cells from SRBC-tolerant animals for the BRBC-PFC was lower than that of normal BM cells or it was completely absent. The implications of these findings for the mechanism of the stimulating BM activity are discussed.

Animals↗
PubMed1979

Xenogeneic bone marrow stimulating effect in vitro on antibody-producing cells.

It was described earlier that in the tissue cultures of immune mouse LN cells the number of antibody producing cells was increased 2-3-fold when syngeneic of allogeneic nonimmune BM cells were included in the cultures. In these experiments, parallel mixed cultures were set up of mouse immune LN cells with non-immune BM cells of either syngeneic or xenogeneic origin (rat, pig and chicken). Xenogeneic BM also increased the number of PFC in the mixed cultures. The intensity of the stimulation effected by xenogeneic BM of all three species tested was comparable to that induced by syngeneic BM. The number of PFC in all types of the mixed cultures was significantly higher (P less than 0.005) than in the LN cell cultures alone. The differences between the effect of syngeneic and xenogeneic BM and between the xenogeneic BM cells of different origin were not statistically significant (P less than 0.05).

Animals↗