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J M Rojo

Publications and source records attributed to J M Rojo.

49 records · Page 3Linked to original sources

Exogenous additions of prostaglandins variably alter the blastogenic response of B and T lymphocytes from different mice lymphoid organs.

Prostaglandins A1 and E2 enhance the 3H-thymidine (TdR) uptake in spleen cell cultures stimulated by two B-lymphocyte mitogens (E.coli lipopolysaccharide (LPS) and dextran sulfate (DXS) at concentrations ranging between 10(-8) and 10(-6) M. The same prostaglandin (PG) concentrations inhibited concanavalin A (Con A) activation of mouse spleen cells depleted or not from a glass-adherent prostaglandin-producing population of suppressor cells. After fractionation of spleen cells by nylon wool adherence, PGs diminished 3H-TdR uptake by nylon nonadherent (T-enriched) cells cultured in the presence of Con A and enhanced the activation of nylon adherent (B-enriched) cells by LPS. The proliferative response of thymic lymphocytes to Con A was drastically inhibited (70-95% by PGE2 10(-8)-10(-6) M. In cultures of purified bone marrow lymphocytes, PGE2 induced a dose-dependent inhibition of either LPS- or DXS-induced activation reaching a 30-40% inhibition at a PGE2 concentration of 10(-6) M. In the spleen, treatment of cells with anti-T sera and complement resulted in abrogation of PG-induced enhancement. Nevertheless, no inhibition of B-cell mitogenesis was observed in the presence of 10(-6) PGE2. From these results, it can be concluded that a different sensitivity of the proliferative response of lymphoid cells to exogenous PGs exists, depending on the subset (T or B) affected and/or the organ used as a source of these cells.

Animals↗

Variations in host defence mechanisms and blastogenesis in chickens and mice after rifamycin treatments.

The immunobiological effect of rifamycins on different experimental models has been comparatively studied in chickens and mice using cyclophosphamide as a reference immunosuppressive agent. "In vivo" treatments with rifampicin and rifamycin SV diminished interferon levels in chickens and mice up to two hours after virus challenge. Mitogen induced blastogenesis was significantly depressed by either "in vivo" (5-50 mg/kg) or "in vitro" (5-20 micrograms/ml) drug treatments, although the activation of B lymphocytes was more easily inhibited than that of T lymphocytes. Primary anti-SRBC immune responses suffered a similar immune suppressive action by rifamycin treatments "in vivo". In every case, cyclophosphamide (10-20 micrograms/ml "in vitro" and 25 mg/kg "in vivo") proved to be the most active immunosuppressant. On the other hand, a remarkable parallelism in the effect of rifamycins in chickens and mice was observed in all the experimental systems used.

Animals↗

Effects of several neuroleptic compounds on the blastogenic response of spleen cells from mice.

The effects of chlorpromazine, haloperidol, clozapine and clotiapine on the mitogenic activation of spleen and bone-marrow cells were investigated. The use of two types of treatments (in vitro with 1.5 to 3 x 10(-3) mM for three days and in vivo with 0.3 mM for four days) permitted the demonstration that chlorpromazine was the most effective drug to inhibit DNA synthesis in mitogen stimulated mouse spleen cell cultures. However, in more prolonged in vivo treatments with a lower dose (0.075 mM for two weeks), clozapine and clotiapine frequently appeared as the most active inhibitors of mitogen-induced lymphoblastic transformation. In any case splenic T lymphocytes were more affected than B cells of the same origin. (3H) TdR uptake in DXS-stimulated bone-marrow cell cultures was also variably inhibited by in vivo drug treatments of mice as compared to groups of untreated animals. Occasionally, the effect of the drugs in vivo depend on the length of the treatment, rather than the dose administered. All these inhibitory effects did not appear as a phenomenon of cytotoxicity since doses used in vitro inhibit by less than 5% the cell viability. It is suggested that the variable depressions of the different mitogenic responses, produced by these neuroleptic drugs, may reflect an alteration in the cyclic AMP levels as a consequence of its inhibition of a phosphodiesterase activator.

Animals↗

Lymphoid-organ variations and blastogenic responses of splenocytes in estrogen-progestogen treated virgin and multiparous mice.

A moderate reduction in size and nucleated cell number was found in spleen and mesenteric lymph nodes from virgin and multiparous female mice on estrogen-progestogen treatment. Whereas the thymus of the multiparous animals did not show any change due to this treatment, the number of bone marrow cells in the treated virgin animals was higher than that in control mice. An enhancement of splenocyte blastogenesis in the presence of Con A, PHA, and LPS was produced by the hormone treatment; it was independent of the age and degree of thymic involution. In DXS-activated lymphoid cells a significant differential behavior was observed; thus a clear depletion of DXS-sensitive lymphocytes was detected in the spleen cell cultures from drug-treated multiparous females.

Aging↗

Variable effects of indomethacin and four related compounds on lymphocyte blastogenesis and cell-mediated cytotoxicity.

Activation of spleen cell cultures by T-cell mitogens appeared enhanced or suppressed by the presence of some nonsteroid anti-inflammatory drugs such as indomethacin and indomethacin esters in a dose-dependent fashion. However blastogenesis of B cells by bacterial lipopolysaccharide was inhibited by the same drugs at every concentration tested. In vivo treatment of mice with indomethacin led to an inhibition of both T and B lymphocyte responses to mitogens. Addition of indomethacin to Concanavalin A-stimulated spleen cells from indomethacin-treated mice further inhibited the response to the mitogen. Indomethacin and indomethacin esters induced only a slight inhibition of cell-mediated cytotoxic reactions when added to cultures, whereas these reactions were markedly inhibited in spleen cells from indomethacin-treated mice.

Animals↗

Further studies on the immunosuppressive effects of indomethacin.

Oral administration of indomethacin inhibited immune response to sheep red blood cells in mice as assessed by direct plaque-forming cells. Serum titers, subsequent to immunization with Pseudomonas aeruginosa lipopolysaccharide, were also diminished in the indomethacin-treated mice. These effects were independent of both the antigen used as well as the magnitude of the primary immune response obtained. Prostaglandins are suggested to play a positive role in in vivo B cell proliferation and function.

Animals↗

"In vivo" effects of acetylsalicylic acid and two ether derived compounds on primary immune response and lymphoblastic transformation.

A comparison was performed of acetylsalicylic acid and two ether derivatives (Benorilate and Eterilate) and indomethacin in order to ascertain the in vivo effects on the lymphoblastic transformation and the primary immune response in mice. The humoral response in Benorilate-and Eterilate-treated mice was 40-50% lower than that of the controls, whereas in acetylsalicylic acid-treated mice the response was only 25% inhibited. The number of immunoglobulin synthesizing cells was neither reduced by acetylsalicylic acid nor by its derivatives, although indomethacin treatments (used for comparative purposes) inhibited by 40% the number of direct plaque-forming cells on the days tested. Mitogen-induced proliferation of spleen lymphocytes was also inhibited in the treated mice; these inhibitions were negligible in the case of cells from acetylsalicylic acid-treated mice activated by concanavalin A and slight in cells from Benorilate-treated mice activated by bacterial lipopolysaccharide. When lymphocytes from drug-treated animals were further cultured in the presence of the same drug, a variable inhibition of mitogen-induced proliferation was observed. These different in vivo effects of acetylsalicylic acid and the two ether derivatives and indomethacin may be due to a distinct action on diverse lymphocyte subpopulations altering their cellular collaborative interactions or modifying the prostaglandin availability.

Acetanilides↗

Effect of indomethacin on in vitro T- and B-cell activation and cell-mediated lysis.

The effect of indomethacin, an inhibitor of prostaglandin synthetase, on lymphocyte blast transformation induced by T- or B-cell activators has been studied. Simultaneously adding indomethacin (0.03-0.3 x 10(-6) M final concentration) and concanavalin A to mouse spleen cell cultures, led to an enhancement of 3H-thymidine uptake, whereas 30 x 10(-6) M indomethacin inhibited this uptake. The stimulation induced by indomethacin was higher when this drug was present in the cultures before the addition of the mitogen. Neither the optimal concanavalin A concentration nor the day on which the maximum of 3H-thymidine uptake occurred were altered by indomethacin. Activation of B lymphocytes induced by bacterial lipopolysaccharide was inhibited by indomethacin at all concentrations tested. However, indomethacin similarly blocked the prostaglandin synthesis as well in lipopolysaccharide- or concanavalin A-stimulated lymphocyte cultures. Indomethacin enhanced the one-way mixed lymphocyte reaction. No significant effect of indomethacin was found on cell-mediated cytotoxicity of 51Cr labeled targets. The results are discussed in terms of differential sensitivity of B and T lymphocytes to this anti-inflammatory drug.

Animals↗

Transfer of antibacterial immunity by "Immune" RNA from animals treated with pseudomonas lipopolysaccharide.

The humoral primary immune response to Pseudomonas aeruginosa lipopolysaccharide was studied. Mice immunized with various doses of LPS developed anti-LPS antibodies. Antibody activity was due to 19S and 7S immunoglobulins. Extracts rich in RNA from spleen cells of immune mice were able to transfer specific anti-LPS response to normal recipients. Immunogenic antigen contamination of RNA was ruled out by a variety of controls.

Animals↗

Indomethacin esters acting as anti-inflammatory and immunosuppressive drugs.

Administration of indomethacin and ten different indomethacin derivatives led to a variable depression in the mice immume response to sheep red blood cells (SRBC) as shown either by direct hemolytic-plaque assay or hemagglutination tests. Compounds with a lower toxicity than indomethacin and predominant immunosuppressive or anti-inflammatory activity were obtained. According to the variations in the primary immune response and to their variable anti-inflammatory actions, the structure-activity relationships are documentted and some possible explanations, relative to their immunodepressive effect, are discussed.

Animals↗

Sodium diethyldithiocarbamate restores T lymphocyte proliferation, interleukin-2 production and NK activity in cyclophosphamide-immunosuppressed animals.

The in vivo effect of sodium diethyldithiocarbamate (DTC) on IL-2 production, mitogen-induced proliferation and natural killer (NK) activity of lymphocytes from normal as well as cyclophosphamide (CY)-treated mice has been investigated. DTC was given in a single subcutaneous injection (25 mg/kg) to normal or cyclophosphamide-treated mice (250 mg/kg i.p. simultaneously to DTC). An enhancement of T lymphocyte proliferation in CY-treated animals and an increase of IL-2 production in both normal and immunosuppressed mice was observed. When DTC (10 mg/kg) was administered daily for two weeks an increase in concanavalin A-induced mitogenesis, IL-2 production and NK activity in CY-treated animals was observed. These immune parameters were reduced 12 days after CY treatment by a factor of 2 to 3 times, while DTC treatment restored these responses to normal levels. LPS-induced mitogenesis was not significantly enhanced. The effect of DTC could be partially mediated by changes in IL-2 activity. According to these results some functional parameters of the immune system of the suppressed host can be partially or completely restored by means of an appropriate immunomodulator treatment. DTC could be of interest in the treatment of diseases where immune functions are impaired or in combined treatments with immunosuppressants.

Animals↗