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Biomedical subjects

L A Fonina

Publications and source records attributed to L A Fonina.

At least 19 recordsLinked to original sources

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↗

[Endogenous immunoregulatory peptides (myelopeptides): structure, function, and mechanism of action].

Previously unknown bioregulators from bone marrow, myelopeptides, were isolated, identified, and synthesized, and their biological properties and mechanism of action were studied in detail. Phe-Leu-Gly-Phe-Pro-Thr (MP-1) manifests an immunocorrecting effect by restoring the level of antibody production in animals suffering from immunodeficiencies of various etiologies; Leu-Val-Val-Tyr-Pro-Trp (MP-2) manifests an antitumor effect by abolishing the inhibitory action of tumor cells on the functional activity of T-lymphocytes; Leu-Val-Cys-Tyr-Pro-Gln (MP-3) stimulates phagocytosis by macrophages and, in this way, protects animals from infections caused by pathogenic microorganisms; and Phe-Pro-Arg-Ile-Met-Thr-Pro (MP-4) is a new factor of cell differentiation inducing terminal cell differentiation in the HL-60 and K-562 leukemic cell lines.

Adjuvants, Immunologic↗

[Myelopeptides: isolation and structure].

A new method was developed for the isolation of biologically active peptides present in small quantities in supernatants of bone marrow cell cultures. Four new peptides, which exhibited immunostimulating and differentiating activities, were isolated from the supernatant using solid phase extraction and reversed-phase HPLC. For these peptides, the following primary structures were elucidated: Leu-Val-Cys-Tyr-Pro-Gln, Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro, Val-Val-Tyr-Pro-Asp, and Val-Asp-Pro-Pro.

Adjuvants, Immunologic↗

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↗

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↗

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↗

The dependence of the conductance and lifetime of gramicidin channels on the thickness and tension of lipid bilayers.

The lifetimes of channels formed by natural gramicidin and its dimeric analog in monoglyceride lipid bilayers of various compositions were investigated. The bilayer surface tension was altered by changing the length of the monoglycerides' fatty acid chain or the chain length of hydrocarbon solvent by isomerization or saturation of the lipid, by varying the amount of solvent in the bilayer, and by changing the salt composition of the aqueous solutions. The logarithms of mean channel lifetimes were found to be proportional to the surface tension of the membrane irrespective of how the surface tension was changed. In contrast, no simple relationship between channel conductance and surface tension or bilayer thickness was found.

Cholesterol↗

[Effect of the SH-group of myelopeptide MP-3 on its macrophage-stimulating activity].

Peptide Leu-Val-Cys-Tyr-Pro-Gln, identical to the bone marrow peptide MP-3, and its Val3 and Ser3 analogs, lacking SH-group, were synthesized by conventional methods of peptide chemistry in solution and, along with the MP-3 S-S-dimerization product, were studied with respect to their effect on the macrophage phagocytic activity. It was shown that the activity was only enhanced by peptide MP-3, which demonstrated the essential role of the SH-group in this function. The dimer analog of MP-3, unlike dimer analogs of other monocysteine-containing peptides, glutathione and HP5b, did not exhibit the inhibitory effect.

Amino Acid Sequence↗