摘要:

AbstractImmunological and biochemical markers of leukemia/lymphoma cells have provided valuable insight into hematopoietic malignancy and normal differentiation. The general assumption is that as early lymphoid cells become conmitted towards terminal differentiation they lose their capacity for bimodal differentiation and cells become restricted to B or T cell development and function.We have observed that phenotypically“late”leukemic B cells close to secretory stage can spontaneously expressmature T cell antigens (T11, T4 and T8) after culture in vitro. In further studies of these cells, it was found that the biochemical marker Lactate Dehydrogenase (LD) follows the intermediate pattern expressed by thymocytes rather than that of typical B cells. The expression of T cell antigens can be blocked by incubating these cells with the phorbol ester TPA (12–0-tetradecanoyl phorbol 13 acetate) which promotes unidirectional B cell maturation to plasmacytoid cells in a way that mimics normal B cell differentiation. These observations indicate that presecretory malignant B cells are still programmed to express T cell biochemical and antigenic markers and this expression can be influenced by environmental conditions in vitro.

ISSN:0892-3973    

DOI:10.3109/08923978609028612

出版商:Taylor&Francis    

年代:1986

数据来源: Taylor

摘要:

AbstractProstaglandins of the E series (PGE) have been implicated in many facets of immunoregulation, as well as having a possible role in metastatic dissemination. Variant sublines of the Dunning R3327 rat prostatic adenocarcinoma, differing in growth rate, hormonal responsiveness and in propensity for metastasis, were carried in Fisher×Copenhagen F1 animals. Adherent spleen cells were assayed in vitro for their ability to convert arachidonic acid to prostaglandins of the E series. These glass adherent cells presumably include the monocytic and T cell populations which have been implicated as being immunoregulatory. The results indicated that those spleen cells obtained from animals carrying the metastatic R3327-MAT-LyLu subline tumor converted more arachidonic acid to PGE's than cells derived from animals bearing non-metastatic sublines. Cyclophosphamide therapy did not alter such conversion. Multiple regulatory mechanisms for prostaglandin metabolism are suggested.

ISSN:0892-3973    

DOI:10.3109/08923978609028613

出版商:Taylor&Francis    

年代:1986

数据来源: Taylor

摘要:

AbstractPrevious studies have provided pharmacologic evidence that T lymphocyte function may be regulated in part by the intracellular production of various arachidonic acid (AA) metabolites in response to cellular stimulation. However, the specific AA metabolic capabilities of homogeneous T cell populations have not been clearly defined. In the present studies, we have employed an accessory cell-free T cell line, HT-2, as a model system for the examination of stimulus-induced eicosanoid biosythesis in T lymphocytes. HT-2 cells were biosynthetically labeled with [3H] -AA and challenged briefly with various agents that stimulate the hydrolytic release of AA from cellular phospholipids. The bee venom peptide melittin stimulated a profound AA release response in the cells and the concomitant synthesis of both cyclooxygenase (PGF2α, PGE2and PGD2) and lipoxygenase (5–,12–,15–NTE and possiofy 5–,12-diHITE) metabolites of AA. The formation of PGs was blocked by 5μM indomethacin, demonstrating that this cell line contains cyclooxygenase activity functionally similar to that described in macrophages and other cell types. The high activity of melittin in this system was shown to result largely from a synergy between the peptide itself and a persistent bee venom phospholipase A2contaminant. However, experiments with melittin freed of detectab le phospholipase A2activity by heating, and with synthetic homopolymers of (L)-lysine and (L)-arginine demonstrated that HT-2 cells contain sufficient endogenous, stimulus-responsive phospholipase A2to provide both the cyclooxygenase and lipoxygenase pathways of AA metabolism with substrate. In contrast, Ca++ionophores, which are known to stimulate AA release and metabolism in certain cell types, stimulated only AA release but no detectable eicosanoid biosynthesis in HT-2 cells. Experiments with exogenous bacterial phospholipase C suggested that this cell line can also generate free AA for eicosanoid biosynthesis from membrane-derived 1,2-diacylglycerol. These results indicate that multiple intra-cellular pathways of AA metabolism are present HT-2 cells, and that the stimulus-induced release of AA and the production of eicosanoid second messengers may result from activation of either phospholipase A2or phospholipase C.

ISSN:0892-3973    

DOI:10.3109/08923978609028614

出版商:Taylor&Francis    

年代:1986

数据来源: Taylor

摘要:

AbstractThe immunomodulatory effects of Wy-41,770 (5H-dibenzo[a,d)cyclohepten-5-ylidene)acetic acid, were compared to levamisole and indomethacin in several in vivo models. In the Jerne plaque assay, Wy-41,770 (1 and 100 mg/kg, p.o.) administered on day 1 after sensitization suppressed IgM plaque forming cells (PFC) while levamisole was active when given on days 1 and 2 after sensitization. In contrast, indomethacin administered on days 2 and 3 after sensitization increased PFC. In the rat experimental allergic encephalomyelitis (EAE) model, Wy-41,770 reduced limb paralysis at 10 and 100 mg/kg, p.o. when dosed before sensitization. Indomethacin was active too when predosed in the rat EAE model. In the methylated bovine serum albumin model (MBSA) delayed hypersensitivity (DH) model in mouse, Wy-41,770 (10 mg/kg, p.o.) given on day 1 prior to sensitization and day 2 after sensitization in subliminally sensitized animals augmented the DH response while inhibiting the subliminal DH response when administered at 6 hr after challenge. Levamisole showed similar activity in this subliminal model while indomethacin given 6 hr post challenge was inhibitory. All three drugs were inactive in mice normally sensitized to MBSA at the same drug regimens. In guinea pigs, subliminally sensitized to tuberculin, Wy-41,770 (10 and 100 mg/kg, p.0.) and levamisole augmented the DH response. No changes in DH response were observed for both drugs in normally sensitized guinea pigs. In the rat adjuvant arthritic model, Wy-41,770 (5 and 15 mg/kg, p.o.) inhibited day 16 uninjected paw edema and restored significantly the depressed proliferative responses to mitogen by spleen cells taken from the same arthritic rats at day 16. The moderate immunomodulatory activity of Wy-41,770 may contribute along with its antiinf lammatory activity, towards the treatment of arthritic diseases.

ISSN:0892-3973    

DOI:10.3109/08923978609028615

出版商:Taylor&Francis    

年代:1986

数据来源: Taylor

摘要:

AbstractThe effect of benzo(a)pyrene (BaP) at different molar (MI concentrations on the in vitro anti-sheep red blood cell (SRBC) plaque (antibody) forming cell (PFCI response and the one-way mixed lymphocyte response (MLR) was tested. Inhibition of the PFC response and the MLR occurred when spleen cells were exposed to a wide range of BaP concentrations from 10–4m to 10–8m. Maximum depression of the responses occurred at 10–5M for PFC production (47% of controls) and for the MLR (19% of controls) as measured by a stimulation index. No significant loss in cell viability was observed at this or lower molar concentrations of BaP. The non-carcinogenic analog of BaP, benzo(e)pyrene, did not suppress PFC responses at comparable concentrations. This in vitro system will facilitate manipulations of T and B lymphocytes and macrophages (adherent cells) in a controlled culture environment for precisely characterizing the sensitivity of these cells and their subpopu-lations on exposure to BaP.

ISSN:0892-3973    

DOI:10.3109/08923978609028616

出版商:Taylor&Francis    

年代:1986

数据来源: Taylor

摘要:

AbstractAdministration of urethan (LTRE or ethyl carbamate) to mice results in the development of a variety of tumors, and, in certain strains of mice, marked suppression of the immune response. Perinatal exposure of mice to URE has been found to result in increased tumor induction compared to exposure of adult animals. In the present study, the effects of perinatal exposure to UKE on the development of immunorompetence was investigated. Pregnant mice were injected with total doses of either 0.5 or 1.0 mg URE/g of body weight over days 7–16 of gestation or pups of nontreated dams were administered a total dose of 2.0 mg URE/g of body weight over postpartum days 5–14. Postnatal exposure to URE suppressed NK (natural killer) cell activity but left intact other measured parameters of the host defense system. Prenatal exposure, on the other hand, resulted in elevated leukocyte counts and a trend toward increased spleen and thymus size in offspring of treated mothers. Humoral immune function, as measured by the IgM response to sheep erythrocytes, was suppressed in pups from dams injected with a total of 1.0 mg/g URE. These results indicate that marked differences in immunopharmacologic effects may be observed if chemical exposure occurs at different times during the ontogeny of the immune system.

ISSN:0892-3973    

DOI:10.3109/08923978609028617

出版商:Taylor&Francis    

年代:1986

数据来源: Taylor

摘要:

AbstractFive multiple sclerosis patients were treated weekly with cytosine arabinoside (araC) on an escalating dose schedule. The dose was initiated at 50mg/M2and then increased once each week by 50mg/M2(unless toxicity caused delay). Dosage decisions were based on whether or not the antibody-dependent cellular-cytotoxicity (ADCC) or natural killer (NK) cytotoxicity levels had been reduced to a level more than 2 standard deviations below the control range. Cytosine arabinoside treatment was discontinued in 2 of 5 subjects at doses of 500mg/M2due to toxicity. The 3 remaining patients demonstrated sustained reductions in the percentage of FcR+cells in their peripheral blood. The maximum percentage reductions from the baseline values ranged from 50% to 76%. Concomitant reductions in the NK activity at the same doses ranged from 65% to 83%. ADCC activity in all 3 patients, however, was relatively resistant to suppression. The nadirs for the ADCC activity were only 16% to 44% below the baseline minimums. AraC was shown to reduce the proportion of FcR+cells and NK cytotoxic activity in preference to ADCC activity.

ISSN:0892-3973    

DOI:10.3109/08923978609028618

出版商:Taylor&Francis    

年代:1986

数据来源: Taylor

摘要:

AbstractThe therapeutic effect of endogenous tumor necrosis factor (TNF) on Meth A ascites fibrosarcoma in mice was investigated. Serum and peritoneal fluid from tumor bearing mice treated with OK-432 and LPS were cytotoxic to tumor cells in vitro. The peak of cytotoxicity in both the serum and peritoneal fluid was found in the fraction corresponding to a molecular weight of approximately 54,000–56,000 on HPLC and the PI was found to be 4.9–5.1 by is oelectric focusing. These results are consistent with previously reported findings on TNF, and indicate that endogenous TNF has a satisfactory life-prolonging effect.The tumor necrosis factor (TNF) is considered to be one of the clinically most promising anti-cancer cytokines because of its potent and very specific antitumor effect on target cells (Carswell, Old, Kassel, Green, Fiore&Williamson, 1975; Matthews&Watkins, 1978; Niitsu, Watanabe&Urushizaki, 1984).TNF as an anti-cancer cytokine for the treatment of cancer may be applied in one of the two following ways: 1) by administration of purified TNF or 2) by endogenously inducing TNF in cancer bearing individuals. The antitumor effects of TNF administered exogenously have been examined using crude preparations or serum containings TMF (tumor necrosis serun, TNS) (Carswell et al., 1975; Watanabe, Niitsu, Sone, Neda, Ishigaki&Urushizaki, 1984).In a previous paper we reported that mice primed with OK-432 and challenged with endotoxin produced a soluble cytotoxic factor in peritoneal fluids (Yamamoto, Nagamuta, Usami, Sugawara, Watanabe, Niitsu&Urushizaki, 1985; Nagamuta, Yamamoto, Usami, Sugawara, Watanabe, Niitsu&Urushizaki, 1985).This peritoneal cytotoxic factor (PCF) had cytostatic and/or cytotoxic effect not only on mouse tumor cell lines but also on human tumor cell lines without species specificity. Normal cell lines were not affected. Here we report the endogenous production of TNF in tumor bearing mice and its antitumor effects.

ISSN:0892-3973    

DOI:10.3109/08923978609028619

出版商:Taylor&Francis    

年代:1986

数据来源: Taylor