Regulation of the peritoneal macrophage functional activity by the MP-5 and MP-6 myelopeptides under stress.

In mice, two-hour immobilization stress inhibited zymosan-induced production by macrophages of the oxygen radicals and cytokine IL-1ß. After myelopeptides MP-5 and MP-6 were administered into mice, the stress-induced inhibition of the reactive oxygen species (ROS) and IL-1ß was abrogated. MP-5 peptide stimulated spontaneous ROS production by macrophages and reduced IL-10 production under stress. Thus, under in vivo conditions and under stress, the effect of MP-5 and MP-6 myelopeptides modulates the peritoneal macrophage activity.

[Effects of myelopeptide-1 on functional activity of murine phagocytes treated with cyclophosphan].

The effects of bone marrow derived myelopeptide-1 (MP-1) on functional activities of normal murine phagocytes and phagocytes obtained from mice treated with cytostatic agent cyclophosphan (CY) were studied in vivo and in vitro. We demonstrated immunocorrecting effect of MP-1 on functional activity of bone marrow and peripheral blood phagocytes. An optimal protocol of MP-1 injections during cytostatic therapy was developed to obtain maximal efficacy in immunocorrection. The best effect on functional activity of phagocytes of different localization (the highest effect on peripheral blood neutrophils) was found when MP-1 was injected before CY. The results demonstrated that MP-1 can be considered as a substance able to protect peripheral blood phagocytes from CY damage during cytostatic treatment.

[Synthesis and anti-tumor properties of myelopeptide MP-1].

We have studied anti-tumor properties of bone marrow derived peptide Phe-Leu-Gly-Phe-Pro-Thr (MP-1) synthesized by classical methods. It was shown that MP-1 enhanced the effect ofcytostatic therapy of lymphatic leukemia P388 and increased latent growth period of P388 tumors implanted in irradiated mice. MP-1 also decreased metastasis of mouse breast adenocarcinoma Ca-755 after surgery.

[Synthesis and properties of the myelopeptides with differentiating activity].

The bone marrow myelopeptides Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro (MP-4) and Val-Asp-Pro-Pro (MP-6) have been synthesised by a classical method and by a solid phase synthesis. The differentiating activity of MP-4 and MP-6 in human leukemia cells HL-60 and K-562 has been studied. Both peptides induce terminal differentiation of these cell lines but the mechanism of action of peptides MP-4 and MP-6 is distinguished.

Myelopeptide-5 abolishes virus-induced immunosuppression by restoring T cell functions.

Myelopeptide-5 (MP-5; synthetic analog of endogenous low-molecular-weight peptide Val-Val-Tyr-Pro-Asp) neutralized the immunosuppressive effects of antiviral vaccines (influenza, measles, and measles/parotitis) and stimulated their immunogenicity by restoring functional activity of T cells, suppressed by the viruses. Specific binding of MP-5 to CD4(+) lymphocyte (its target cell) was studied using [(3)H]MP-5 (dissociation constant 2.03 x 10(-7) M).

[Fluorescently labeled differentiating myelopeptide-4: specific binding to and penetration into target cells].

Myelopeptide-4 (MP-4) (Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro), inducing the terminal differentiation of HL-60 leukemia cells, was labeled with fluorescein isothiocyanate. The specific binding of this modified peptide to the surface of HL-60 cells and its ability to penetrate into the cells were studied. It was shown by cytometry and confocal microscopy to be bound on the HL-60 cell surface, to penetrate into their cytoplasm, and finally to concentrate around the cell nucleus. These phenomena are probably necessary for the exhibition of MP-4 differentiating activity.

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.

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.

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.

[Prevention and correction of stress-induced immunodeficiency by atrial electroacupuncture]. / Profilaktika i korrektsiia vyzvannogo stressom immunodefitsitnogo sostoianiia metodom aurikuliarnoi élektroakupunktury.

Secondary immunodeficiency characterized by a sharp decrease in the number of antibody-forming cells in the lymph organs developed in mice under conditions of an immunosuppressive effect of swim stress and hypobaric hypoxia. Auricular electroacupuncture (AEAP) preceding swim stress blocks its immunosuppressive effect completely. AEAP possesses a high preventive action and also produces a marked corrective effect in development of stress-induced immunodeficiency. For instance, AEAP applied in the productive phase of the immune response restores effectively immunocompetence of the body subjected to hypobaric stress. In applying AEAP, the coefficients of antibody-production stimulation in the cells of the lymph nodes, calculated in relation to the hypoxic control, are 3.5-4.0, which do not yield to the values recorded with the use of the most effective pharmacological immunomodulators. AEAP may be considered a promising measure for the prevention and correction of immunodeficiency caused by stress.