ISSN:1660-5527    

DOI:10.1159/000210974

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Fibroblast-dependent differentiation and proliferation of mast cells were reviewed from the viewpoint of mast cell-deficient mutant animals. Mice of W/Wv, Sl/Sldor mi/mi genotype are deficient in mast cells. However, since T cell-dependent differentiation and proliferation of mast cells are intact in these mutant mice, mast cells do develop when bone marrow cells of these mutant mice were cultured in the presence of T cell-derived growth factors. Cultured mast cells (CMC) of W/Wvmice cannot receive the prohferative stimulus from fibroblasts whereas fibroblasts derived from Sl/Sldembryos cannot provide normal (+/+) CMC with the prohferative stimulus. The W locus encodes a tyrosine kinase receptor and the SI locus the ligand for the receptor. Although +/+ CMC acquire the phenotype resembling connective tissue-type mast cells when cocultured with fibroblasts in medium containing T cell-derived growth factors, mi/mi CMC do not. We recently found a mast cell-deficient mutant of rats. Biological features of the mast cell-deficient rats were very similar to those of W/Wvmice. The mast cell-deficient mutant animals are invaluable tools for investigations of differentiation/proliferation and functions of mast cells.

ISSN:1660-5527    

DOI:10.1159/000210977

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Among non-B, non-T cells in the spleen and among unfractionated bone marrow cells, there is a population of cells that are capable of producing IL-4 in response to cross-linkage of FcεRI or FcγRII. Their IL-4-producing capacity is strikingly enhanced by treatment of the cells or of the animals donating such cells with interleukin-3 (IL-3). FcεR+ cells constitute 1–2% of splenic non-B, non-T cells and of bone marrow cells from normal donors but they contain all the capacity to produce IL-4 in response to cross-linkage of FcεRI or FcγRII or to treatment with ionomycin. FcεR- cells fail to make such responses. Electron-microscopic analysis indicates that virtually all the granulated or vacuolated FcεR+ cells are of the basophil lineage. However, it has not yet been resolved whether these cells or immature mast cells, presumably in the FcεR+ granule/vacuole-negative cell population, are the principal producers of IL-4 in response to thes

ISSN:1660-5527    

DOI:10.1159/000210978

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The cytotoxic action of various prostanoids was examined on a transformed human epidermal cell line (HSC-1), and methyl(5S,6S,7Z)-5,6-diacetoxy-7-((2S)-4-chloro-2-hydroxy-2-((2Z)-2-octenyl)-5-oxo-3-cyclopentenylidene)heptanoate (YM-11), which is a punaglandin compound, was found to be most active. YM-11 exerted a dose-dependent inhibition of HSC-1 cell growth over 0.03 μM (0.01 μg/ml), and at 0.3 μM(0.1 μg/ml) its growth was completely inhibited. The IC50 value of YM-11 on HSC-1 cell growth was calculated as 0.15 μM(0.05 μg/ml). Methyl(E)-7-(5-chloro-2-hydroxy-2-octyl-5-oxo-3-cyclopentenylidene)heptanoate (YM-3), which is also a punaglandin derivative, showed remarkable cytotoxicity on HSC-1 cells with an IC50 of 0.24 μM(0.08 μg/ml). Concerning other cytotoxic prostaglandins (PGs), the IC50 values of Δ7-PGA1, Δ12-PGJ2 and PGD2 were 1.5 μM (0.5 μg/ml), 2.1 μM(0.75 μg/ml) and 5.7 μM (2 μg/ml), respectively. On the basis of the present data and previous in vitro and in vivo evidence, punaglandin derivatives may be useful antineoplastic agents for skin cancer.

ISSN:1660-5527    

DOI:10.1159/000210918

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

13-cis-Retinoic acid is a stereospecific suicide inhibitor of thioredoxin reductase. [3H]-labeled 13-cis-retinoic acid has been used to covalently label thioredoxin reductase in human keratinocytes. The acid-soluble cytosol fraction of human keratinocytes contained three radioactive proteins labeled by the addition of high-specific-activity [3H]-13-cis-retinoic acid to cell cultures. One of these proteins was identified as cytosolic keratinocyte thioredoxin reductase by fast-protein liquid chromatography and SDS-gel radioautography. The inhibition of thioredoxin reductase by 13-cis-retinoic acid may explain the known cytostatic and teratogenic properties attributed to this retinoid.

ISSN:1660-5527    

DOI:10.1159/000210919

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Mast cells of the human skin not only release mediators following immunological activation, but may also be stimulated to release histamine by the neuropeptides substance P, vasoactive intestinal polypeptide and somatostatin or by other basic secretagogues such as morphine, poly-L-lysine and compound 48/80. Release of histamine under these conditions is rapid and accompanied by minimal generation of the eicosanoids, prostaglandin (PG)D2 and leukotriene (LT)C4. Transient elevations of intracellular calcium are associated with mediator secretion induced by both stimuli, that induced by anti-IgE being derived from extracellular sources through channels in the plasma membrane while that stimulated by neuropeptides is mobilized intracellularly. Similarly, elevations of intracellular cyclic adenosine monophosphate (AMP) induced by anti-IgE occur only in the presence of extracellular calcium whereas with substance P elevations are apparent even in the absence of extracellular calcium. With the latter stimulus, histamine release is complete before the peak cyclic AMP is achieved. Histamine release stimulated by both secretagogues is unaffected by sodium cromoglycate or nedocromil sodium but is reduced by both salbutamol and isobutylmethylxanthine. Despite these biochemical and temporal differences, degranulation induced by both secretagogues proceeds by compound exocytosis which is indistinguishable under the electron microscope.

ISSN:1660-5527    

DOI:10.1159/000210980

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The kinetics and extent of uptake of ciclosporin (CSA) in various strata of human cadaver skin upon topical application of several CSA formulations were determined by in vitro diffusion cell experiments. The CSA formulations tested included an oil-in-water emulsion and four liposomal systems. The accumulation of CSA in the stratum corneum at 24 h is in the order: ‘skin lipid’ multilamellar liposomes (MLV) > phospholipid MLV ≈ ‘skin lipid’ large unilamellar liposomes (LUV) > phospholipid LUV > > > emulsion. The total amount of drug in the deeper stratum corneum and deeper skin strata at 24 h is in the order: phospholipid MLV > ‘skin lipid’ MLV > phospholipid LUV > ‘skin lipid’ LUV > emulsion. Whereas ‘skin lipid’ liposomes were more effective than phospholipid-based liposomes in depositing drug in deeper skin strata for rodent species (mouse and guinea pig), the opposite effect was observed for human cadaver skin. More importantly, all the liposomal formulations tested were far more effective than the emulsion formulation in depositing CSA into the skin.

ISSN:1660-5527    

DOI:10.1159/000210920

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Elicitation of delayed-type hypersensitivity (DTH) responses is due to the required sequential action of two different antigen (Ag)-specific Thy-1+ cells: early acting, DTH-initiating cells and locally recruited CD4+, αβ-TCR+, DTH effector T cells. DTH-initiating cells have an unusual phenotype for Ag-specific cells (Thy-1+, CD5+, CD4-, CD8-, CD3-, slg-, B220+ (CD45RA+), Mac 1+, IL-2R- and IL-3R+) and act by producing Ag-specific non-IgE factors that sensitize mast cells for release of the vasoactive amine serotonin (5HT) at the local site of elicitation of DTH by challenge. Another mechanism of DTH initiation involves Ag-specific IgE antibodies that also can sensitize mast cells for local serotonin release. Serotonin initiates DTH by activating the local endothelial cells to allow recruitment of DTH effector T cells, and also by activating 5HT-2 receptors on these recruited T cells.

ISSN:1660-5527    

DOI:10.1159/000210981

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000210921

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Cytochalasin D, colchicine or vinblastine effectively inhibited both histamine release and 45Ca uptake induced by compound 48/80 in rat mast cells. The inhibitory effects of cytochalasin D or colchicine on histamine release were exerted more remarkably when permeabilized mast cells were stimulated with either Ca2+ or inositol-1,4,5-trisphosphate (IP3). Since colchicine, vinblastine or cytochalasin D were not effective in inhibiting IP3 formation, it was assumed that microtubules or microfilaments may not participate in the initial stages of the membrane events leading to histamine release. By contrast, in Ca2+ release from the intracellular Ca store both colchicine and vinblastine (but not cytochalasin D) were effective in inhibiting Ca2+ mobilization, indicating that microtubules, rather than microfilaments, are intimately related to Ca2+ release from the endoplasmic reticulum (ER). By means of a fluorescence microscope, it was revealed that colchicine decreased the fluorescence intensity of FITC-labeled anti-tubulin antibody in the mast cells, while the amount of tubulin polymer in mast cells increased after exposure to compound 48/80. The findings indicate that colchicine simply suppressed polymerization of tubulin, while the rearrangement of microtubules so as to increase the polymerization took place after exposure to compound 48/80. Using an electron microscope in combination with potassium antimonate technique, Ca-antimonate dots were clearly observed in a cluster on the surface of the ER and a distinct connection between the ER and microtubules was also observed. It was concluded that microtubules play an important role in the processes leading to Ca2+ release from the intracellular Ca store and in subsequent histamine release.

ISSN:1660-5527    

DOI:10.1159/000210982

出版商:S. Karger AG    

年代:1991

数据来源: Karger