Activated lymphocytes produce mediators potentiating the antitumor cytostatic activity of bone marrow cells

Mitogen-activated murine T and B lymphocytes produce soluble mediators that potentiate the inhibitory effect of bone marrow cells on the growth of leukemic cellsin vitro. γ-Interferon is a T-cell product increasing the cytostatic activity of bone marrow cells. An increase in the cytostatic activity under the effect of T-cell soluble mediators was characteristic of bone marrow cells fromnude mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 63–65, January, 1999     

Production of transmitters stimulating antitumor cytostatic activity of bone marrow cells by activated lymphocytes

Murine lymphocytes preactivated with mitogen (both T and B) produce soluble transmitters which stimulate cytostatic activity of normal mouse bone marrow cells, tested byin vitro inhibition of P815 mastocytoma and L1210 lymphoma cell growth. γ-Interferon is one of T-cell products stimulating antitumor activity of bone marrow cells. Cytostatic activity stimulated by T-cellular soluble transmitters is another characteristic of bone marrow cells isolated from nude mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 6, pp. 660–662, June, 1998     

Opposite effects of dexamethasone on antitumor and natural suppressor activities of bone marrow cells

Effects of dexamethasone on the ability of nonadherent bone marrow cells to inhibit proliferation of mastocytoma P815 cells and concanavalin A-stimulated proliferation of syngeneic splenocytes were studied. Antitumor activity of cells increased, but their natural suppressor activity decreased in the presence of dexamethasone. Pretreatment with dexamethasone (for 3 h) did not affect the sensitivity of mastocytoma cells to antitumor factors and the antitumor activity of bone marrow effectors. Pretreatment of bone marrow cells with dexamethasone for 24 h potentiated antitumor activity of their nonadherent fractions. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 4, pp. 459–461, April, 2000     

Decrease of antitumor and suppressor activities of nonadherent bone marrow cells by culturing in medium conditioned with ehrlich adenocarcinoma cells

It was demonstrated that proliferation of bone marrow cells cultured in medium conditioned with tumor cells is somewhat increased. A much more potent stimulation of bone marrow cell proliferation is observed after the removal of cells carrying the erythroblast antigen. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. N ^o 5, pp. 514–517, May, 1994 Presented by N. V. Vasil'ev, Member of the Russian Academy of Medical Sciences     

Differential induction of natural suppressor activity of bone marrow cellsin vitro by different types of tumors

The suppressor activity of bone marrow cells not adhering to plastic is shown to appreciably increase after their 48-hour joint preincubation with mastocytoma P-815 supernatant or WEHI-3 myelomonocytic strain and to be unchanged after incubation with dupernatants of K-2 erythroleukemic strain or Ehrlich's ascitic carcinoma. P-815, WEHI-3, and K-2 tumors are shown to produce factors characterized by colony-stimulating activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 8, pp. 184–187, August, 1995 Presented by N. V. Vasil'ev, Member of the Russian Academy of Medical Sciences     

Antitumor activity of normal bone marrow cells

After separation of normal murine bone marrow cells in a Percoll density gradient cellular fractions with densities of 1.076 and 1.060 g/ml are capable of suppressing thein vitro growth of leukemia cells. The cytostatic activity of these fractions, however, does not surpass the level of antitumor antiproliferative activity intrinsic to intact bone marrow cells. These cells were found to be capable of joining the splenocytes, thymocytes, and lymph node cells in effector cytostatic cooperation and thus enhance the final antitumor effect. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 8, pp. 181–183, August, 1995     

Suppressive and antitumor activities of bone marrow cells and splenocytes of AKR mice during aging

In 4-month-old leukemia-prone AKR mice, the ability of bone marrow cells to inhibit proliferation of concanavalin A-stimulated splenocytes and mastocytoma P815 cellsin vitro was sharply increased in the preleukemic period. In 7-month-old mice, differences in natural suppressive activity of bone marrow cells were significant, but less pronounced than in 4-month-old mice. The immunosuppressive activity was not found in the spleen. In 4-month-old AKR mice, in the inhibition of proliferation of mitogen-stimulated splenocytes was increased due to enhanced NO production by bone marrow cells. These findings suggest that the increased antiproliferative activity observed in the bone marrow of AKR mice long before the appearance of clinical manifestations of leukemia is associated with disturbances in differentiation of myeloid progenitor cells and accumulation of natural suppressor cells in the bone marrow. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 452–454, April, 1999     

Suppressive activity of bone marrow cells from patients with stomach cancer. Effect of prostaglandins, transforming growth factor-β, and nitric oxide

It is shown that nonadhesive bone marrow cells from patients with stomach cancer suppress phytohemagglutinin-stimulated proliferation of peripheral blood lymphocytes of healthy donors and proliferation of Molt-4-human lymphoma cellsin vitro. Suppressive activity of bone marrow cells from cancer patients is not mediated through prostaglandin secretion, since indomethacin has no effect on it. Addition of neutralizing monoclonal antibodies to transforming growth factor-2₁, 2₂, and 2₃ partially reduces this suppressive effect. Suppressive effect of bone marrow cells from patients with stomach cancer is partially mediated through production of nitric oxide, since the inhibitor of its synthesis N⁹-monomethyl-L-arginine diminishes the inhibiting effect of bone marrow cells from cancer patients on phytohemagglutinin-stimulated proliferation of peripheral blood T cells from healthy donors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 2, pp. 217–220, February, 1998     

Suppression of antibody formation by bone marrow T cells activated by histocompatibility antigens

The suppressive action of bone marrow T cells activated by histocompatibility antigens on antibody formation was studied. The bone marrow of CBA mice was shown to contain thymus-dependent lymphocytes which, on hyperactivation by repeated transplantation into F₁ recipients, have a suppressive action on the development of the cooperative immune response to sheep's red cells. Preliminary treatment of the bone marrow cells with antithymocytic globulin and complement abolished the suppressive effect.Institute of Biophysics, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Sciences of the USSR, P. D. Gorizontov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 300–302, March, 1977.     

Role of interferon-γ in regulation of antiproliferative activity of bone marrow nonadherent cells

Bone marrow nonadherent cells were cultured for 3 days with supernatants of concanavalin A-stimulated splenocytes containing interferon-γ, whose activity was estimated by the ability to induced NO production. Supernatants with a high inducing activity decreased natural suppressor activity of bone marrow nonadherent cells and production of NO, but the activity of the supernatant of these cells increased. Inhibition of NO production during treatment with these supernatants prevented the decrease in suppressor activity; production of NO then increased. Supernatants with a low inducing activity increased natural suppressor activity of bone marrow nonadherent cells but not NO production. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 677–680, December, 1999     

Importance of the time of bone marrow transplantation for manifestation of allogeneic inhibition of stem cells

The effect of duration of the interval (4–96 h) between irradiation of F₁ (CBA×C57BL/6) hybrids and transplatation of bone marrow from C57BL/6 mice on manifestation of allogeneic inhibition of the stem cells was studied. In this particular donor-recipient model the degree of allogeneic inhibition was 90%. Transplantation of bone marrow carried out 4–48 h after irradiation had no effect on the number of colonies in the spleen of the F₁ hybrids. Considerable abolition of allogeneic inhibition (33%) was observed if the parental cells were injected 96 h after irradiation. Remote transplantation had no effect on the number of colonies in the spleen of syngeneic recipients.Laboratory of Experimental Genetics, Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 3, pp. 347–348, March, 1976.     

Resistance of the suppressor function of T cells to agents with antiproliferative activity

Injection of cyclophosphamide (CP) in a dose of 50–400 mg/kg into mice immunized with sheep's red blood cells (SRBC) does not significantly reduce the ability of the spleen cells of these mice to suppress the primary immune response when transplanted into intact syngeneic recipients. Irradiation of the donors of immune spleen cells (ISC) in a dose of 900 R or treatment of the ISC in vitro with mitomycin C did not affect their suppressor activity. The supernatant (SN) obtained after ultracentrifugation of sonicated ISC inhibited the primary immune response of intact mice. It is concluded that the suppressor effect of ISC is due to a factor produced by the T cells; active proliferation of these cells is not essential for the realization of its action.Laboratory of Immunogenetics, Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 9, pp. 327–330, September, 1977.     

Effect of radon on dendritic cells of the central lymph and on process-forming bone marrow cells of rabbits

The phenotypic parameters of dendritic cells of the central lymph and of red marrow cells with processes in rabbits are compared using the light-optical and morphological methods and an original technique of lymph sampling. The effect of radon on the time course of the number of the above-mentioned cells is explored. Two major types of cells with processes are identified in the red marrow: cells with one process and cells with two or more processes. These cells and the corresponding types of dendritic cells of the central lymph are not identical, which does not rule out their common origin. the number of above-mentioned cells correlates with the activity of radon. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 7, pp. 102–103, July, 1994 Presented by Yu. I. Borodin, Member of the Russian Academy of Medical Sciences     

Hybrid resistance of bone marrow stroma to precursor cells

The focus of hematopoiesis arising after transplantation of a fragment of bone marrow from a C57BL mouse beneath the capsule of the kidney of a syngeneic mouse contains more hematopoietic cells than if transplanted into a semisyngeneic (CBA x C57BL)F₁ recipient. Experiments with repopulation of the graft, when depopulated by irradiation, by injected hematopoietic cells of the same genotype as the graft (C57BL) showed that these differences are due to the smaller size of the hemotopoietic microenvironment in the focus formed in the hybrid than in the syngeneic system. Hybrid resistance is thus manifested not only against hematopoietic cells, but also against stromal precursors transferring the hematopoietic microenvironment.Laboratory of Cultivation and Transplantation of Bone Marrow, Central Institute of Hematology and Blood Transfusion, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Fedorov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 339–342, March, 1977.     

Proliferative ability of nucleated rat bone marrow cells after freezing and thawing

The proliferative power of rat bone marrow myelokaryocytes after freezing and thawing under the protection of hydroxyethyl derivative of tetrahydric alcohol (HEDTA) was studied in experiments on mouse-rat radiation chimeras. Rat bone marrow cells were shown to preserve their proliferative power.Institute of Problems in Cryobiology and Cryomedicine, Academy of Sciences of the Ukrainian SSR, Khar'kov. (Presented by Academician of the Academy of Medical Sciences of the USSR A. I. Strukov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 472–474, April, 1977.     

Circulating serum interferon andits effect on the activity of human natural killer cells

The interferon content in the plasma of 6 healthy donors and 10 patients with multiple sclerosis and the effect of an 1-h treatment of mononuclear cells with autologous plasma on their natural killer activity are studiedin vitro using³H-uridine-labeled (3 μCi/ml) human erythromyeloleukosis cells K-562. The serum interferon content in healthy donors is 2.3±0.82 IU/ml, whereas that in patients is higher: 5.2±0.8 IU/ml. Autologous plasma does not affect the activity of natural killer cellsin vitro, whereas it increases the cytotoxicity of mononuclear cells obtained from patients with multiple sclerosis by 35–64%. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 619–622, December, 1994 Presented by S. V. Prozorovskii, Member of the Russian Academy of Medical Sciences     

Deliberate modification of the specific activity of leukemic cells

A comparative study was made of the efficacy of various types of deliberate modification of the leukemogenic activity of a transplantable line of bone marrow cells obtained from animals infected with Rauscher leukemia virus. Treatment of the leukemic cells with neuraminidase, or culturing them at a supraoptimal temperature led to complete loss of their leukemogenic activity, as shown by survival of 100% of the experimental animals and the absence of splenomegaly. Meanwhile, treatment of the cells with concanavalin A and 5-bromodeoxyuridine delayed the development of splenomegaly and lowered the mortality among the recipient animals by 70 and 20%, respectively. The results suggest that these methods of action on leukemogenic cells can be used in order to obtain material for subsequent immunization.Department of Virology, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. D. Solov'ev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 448–449, April, 1977.