摘要:

AbstractThe effect of the opioid agonist morphine and of the (-) and (+) stereoisomers of the antagonist naloxone were studied on superoxide generation from human granulocytes. Morphine or naloxone had no effect on basal or phorbol 12-myristate 13-acetate (PMA)-stimulated superoxide generation. Combined equimolar (-)naloxone and morphine concentrations (0.1 pM - 0.1μ;M) inhibited PMA-stimulated superoxide generation, while combined (+)naloxone and morphine had no effect. The stereospecific effect of naloxone suggests the involvement of opioid receptors. Thus, inhibition of superoxide generation by combined (-)naloxone and morphine could result from the unmasking of non opioid effects of morphine. It is suggested that the opioid control of oxidative metabolism in human granulocytes could involve multiple receptors mediating opposite effects.

ISSN:0892-3973    

DOI:10.3109/08923979209005408

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractThe influence of folic acid and several antagonists of the folic acid metabolism on neutrophil superoxide generation was investigated with the cytochrome c reduction assay. The compounds were found to be partial competitive inhibitors of the NADPH oxidase, their activity apparently increasing with larger substituents at the 10 position. There is evidence that compounds with a 4-oxo substituent are taken up more slowly by neutrophils than those with a 4-amino functionality. Scavenging properties could be excluded from control measurements with the xanthine/xanthine oxidase assay.

ISSN:0892-3973    

DOI:10.3109/08923979209005409

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractConsiderable attention has been directed at defining the health deficits associated with exposure to mercurial compounds. While numerous studies have been conducted, the findings have been somewhat contradictory and have led to a confused understanding of the immunotoxicology of mercury. It is becoming clear, however, that the immunotoxic effects of heavy metals in general, and mercury in particular, are dependent upon the assays and source of cells. The major goal of our study was to assess whether low level mercury exposure modulates human T-cell function. Following treatment of T-cells with HgCl2(0-1000 ng) and MeHgCl (0-100 ng), their activation by mitogens was evaluated. Both forms of mercury caused a dose dependent reduction in T cell proliferation, however, the effect was dependent upon the presence of monocytes. Moreover, in the absence of monocytes, HgCL, enhance PMA induced T-cell proliferation. MeHgCl was approximately 5-10 times more potent than HgCl2. Mercury also inhibited the ability of these cells to synthesize and secrete IL-1. Analysis of the expression of activation markers on the cell surface indicated that one of the earliest markers of lymphocyte activation, CD69, was not effected by mercury. In comparison, T-cell expression of IL-2R and the transferrin receptor was impaired. Of particular interest, cells activated by mitogen for 24 hr became refractory to the immunotoxic effects of mercury. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in T-cell function following exposure to mercury indicates that this metal is immunotoxic at very low exposure levels.

ISSN:0892-3973    

DOI:10.3109/08923979209005410

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractThe major goal of this investigation was to examine the cytotoxic properties of both HgCl2and MeHgCl, in terms of their ability to alter human T-cell and monocyte viability. Following treatment with HgCl2(0-20μ;g/ml) or MeHgCl (0-2μ;g/ml), there was minimal reduction in lymphocyte viability at 1-4 hr. However, after exposure to mercury for 24 hr, cell death was apparent. In comparison, monocytes exhibited significant loss of viability during the early exposure periods. MeHgCl was approximately 5-10 times more potent than HgCl2. Other indicators of cell death were also determined. Measurement of the energy charge ratio indicated profound changes in cellular energy conservation. Electron microscopic analysis of cells treated with mercury revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. In concert with these nuclear changes, there was destruction of cytoplasmic organelles with loss of membrane integrity. Studies of phospholipid synthesis by mercury treated cells confirmed that there were alterations in membrane structure. Thus, there was a decrease in total phosphatide synthesis by treated cells. Moreover, monocyte phospholipid synthesis appeared to be more sensitive to the presence of mercury then lymphocytes. Finally, both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. These morphological and biochemical changes are consistent with the notion that mercury initiates cytotoxic changes associated with programmed cell death.

ISSN:0892-3973    

DOI:10.3109/08923979209005411

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractWe have studied the role of anion channel gating for the autoimmune response in experimental allergic neuritis (EAN) induced by bovine peripheral myelin (BPM). The influence of the stilbene-type anion channel blockers SITS and DIDS on T cell function was assessed by measurement of proliferation and by counting of interferon-gamma (IFN-γ) secreting cells (IFN-γ-sc) in response to BPM and phytohemagglutinin (PHA). SITS caused a dose-dependent increase of spontaneous proliferative activity as well as of proliferation in response to the antigenic stimulus BPM. In contrast, the drug caused a decrease of proliferation of cells stimulated with PHA. The number of cells induced to IFN-γsecretion was reduced by SITS. The suppressive effect was dependent on the degree of activity of cells without drugs. Cultures showing high numbers of BPM reactive T cells were more easily suppressed than cultures with low numbers of BPM reactive T cells. Our results suggest that anion channel gating is involved in the triggering of T cells to IFN-γsecretion. The anion channel signal pathway in lymphocytes could be a target for pharmacological intervention in inflammatory disorders. In the presently used autoimmune model, EAN, the net effect of in vivo treatment with SITS resulted in worsening of clinical signs and increased inflammatory cell infiltration in sciatic nerve, whereas the in vitro conductivity of sciatic nerve was not significantly affected by the drug. Thus anion channel gating seems to regulate activities of immune cells, and drugs with anion channel blocking properties may have effects that enhance autoimmune disease.

ISSN:0892-3973    

DOI:10.3109/08923979209005412

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractThe effect of synthetic peptides - corresponding to the amino acid sequences 289-301 (Y48) and 293-301 (Y91) within the CH-2 domain in the human IgG1 was studied on the oxazolone-specific primary and secondary antibody response isotype distribution and on the sheep erythrocyte (SRBC)-specific primary IgM response. High responder (Ba1b/c) and low responder (C57B1/6) mice to oxazolone hapten were treated intraperitoneally with various doses of peptides simultaneously with the first and second contact sensitization. The relative levels of oxazolone-specific IgM, IgG3, IgG1, IgG2a and IgG2b antibodies were determined by a solid phase radioimmunoassay. Y48 and Y91 peptides in a dose range of 10−5-10−8M/animal enhanced the oxazolone-specific antibody response. This effect was more striking under suboptimal conditions: using smaller antigen dose for sensitization, cyclophosphamide pretreatment or using genetically low responder mice. SRBC-specific primary IgM response was enhanced by Y91 peptide, Y48 was ineffective.

ISSN:0892-3973    

DOI:10.3109/08923979209005413

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractChemotactic responsiveness to fMet-Leu-Phe in concentrations of 10−8to 10−4M in the Boyden chamber was compared between peritoneal exudate cells (PEC) and polymorphonuclear leukocytes (PMN) isolated from peripheral blood, between MRL/Mp-+/+ (MRL-+/+) and MRL/Mp-1pr/1pr (MRL-1pr/1pr) mice, and between young (6 - 9 week old) and aged (16 - 24 week old) mice. Chemotactic responsiveness of PEC did not differ between MRL-+/+ and MRL-1pr/1pr, and young and aged mice. While, PMN showed greater chemotaxis in aged MRL-+/+ mice than that in aged MRL-1pr/1pr mice. These results suggest that chemotactic responsiveness of PMN differ from that of PEC which is assumed to be preactivated by an inflammatory agent injected into the peritoneal cavity to elicit cells. Less responsiveness of PMN to the bacterial origin peptide might relate to the autoimmune disease of this murine model.

ISSN:0892-3973    

DOI:10.3109/08923979209005414

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractComplex patterns of metabolic and functional characteristics are induced in macrophages by biological response modifiers. The study of the early events resulting from the transduction of immunomodulatory signals could be an approach for a better understanding of this activation process. The transcription of c-fos and c-myc genes has been shown to be rapidly modified in many cells responding to various signals. Since murine peritoneal macrophages are a rather heterogeneous population we chose to investigate the c-fos and c-myc modulation in the P388D1 murine macrophage line. Owing to the frequent implication of the c-myc gene in the tumorigenicity of hematopoietic cells we first demonstrated the normal c-myc status in this cell line by Southern analysis. The modulation of the c-fos and c-myc expression has been studied by Northern analysis, 15, 30 and 60 minutes after treatment of the P388D1 cells by the phorbol ester (TPA), the Calcium ionophore A 23187 (Ca2+I), the N-acetyl muramyldipeptide (MDP) or the macrophage Colony Stimulating Factor (CSF-1). The mitogenic activity of these compounds, as evaluated by pH] thymidine incorporation, has been measured either after a 30 minute or a 24 hour treatment.An early increase in c-fos expression always preceded a c-myc augmentation. The highest modulation of c-fos and c-myc was observed with TPA. Ca2+I and TPA presented a low mitogenic effect if compared to CSF-1. MDP did not change DNA synthesis even after 24 hours. Therefore, in the present study on the P388D1 macrophage cell line, no direct correlation could be evidenced between the mitogenic effect and the modulation of c-fos and c-myc induced by these immunomodifiers. Investigations are in progress in order to evaluate the role of these proto-oncogenes on terminal differentiation induced by immunomodulators in this cell line.

ISSN:0892-3973    

DOI:10.3109/08923979209005415

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractMorphine treatment has been shown to suppress several immunologic parameters. In this study, we examined the effects of morphine pellet implantation in vivo on the primary antibody response measured in vitro in various mouse strains. Effects of mouse strain and sex on morphine-induced suppression of the plaque-forming cell response, as well as spleen weight and mortality were determined. Morphine suppressed the primary antibody response in C3HeB/FeJ, C3H/HeJ and C57BI/6 mice, while Balb/cByJ and the (i-receptor-deficient strain CxBk/ByJ mice were not affected. There was no difference in the response to morphine between male and female C3HeB/FeJ mice. Naltrexone reversed the morphine-induced suppression in the C3H strains, but not in C57BI/6 mice. In addition, naltrexone caused significant mortality in Balb/cByJ mice. Spleen weight was decreased by morphine treatment in all the strains, but only the C3H strains were sensitive to the lethal effects of morphine. Thus, immune suppression did not correlate with splenic atrophy or mortality. The strain differences in response to chronic morphine and naltrexone treatment suggest that morphine may be acting through both opioid and non-classical opioid (e.g., not blocked by naltrexone) mechanisms.

ISSN:0892-3973    

DOI:10.3109/08923979209005416

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractMarijuana, and specifically its psychoactive component, THC, can up or down regulate lymphocyte proliferation in murine spleen cells depending in part on the method used to stimulate the cells. This study identifies a difference in THC induced disregulation using cells derived from two different secondary lymphoid organs, the spleen and the lymph node. It was found that THC treatment of mitogen (concanavalin A or phytohemagglutinin) stimulated cells derived from either organ resulted in suppression of the proliferative response. In contrast, spleen cells stimulated with anti-CD3 antibody and treated with low doses of THC displayed an enhanced proliferation whereas the response in lymph nodes did not change. The cell type involved with this THC immunoenhancement in spleen cells was found to be the Ly2 cell. Further differences in the THC modulation of Ly2 spleen cells as compared to lymph node cells were noted following stimulation with PHA. Proliferation of Ly2 cells of splenic origin was inhibited with low doses of THC whereas the Ly2 cells of lymph node origin were more resistant to this drug induced suppression. This study, therefore, demonstrates differences in the immunomodulatory capability of THC dependent upon the organ source of the lymphocytes.

ISSN:0892-3973    

DOI:10.3109/08923979209005417

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor