摘要:

AbstractCotreatment or pretreatment of several human myeloid cell lines (KG1, HL60, U937, THP1) with the differentiation inducer DMSO was found to potentiate the antiproliferative and cytotoxic effects of TNF. In addition, TNF‐resistant monocytic cell lines could be sensitized to TNF cytotoxicity by DMSO treatment. Other highly polar molecules, known to be potent differentiation inducers, showed similar effects to those of DMSO. The potentiating effect of DMSO was related neither to an up‐regulation of TNF receptor expression nor to an alteration in the rate of TNF internalization and degradation. We present evidence that the TNF activities are p55 TNF receptor‐mediated and are not due to insertion of TNF into lipid bilayers, an effect that could be susceptible to DMSO, as this component has been described to modify cell membrane characteristics. DMSO‐induced potentiation of TNF cytostasis/cytotoxicity was restricted to myeloid leukemia cell lines. In non‐myeloid cells such as fibrosarcomas, myosarcomas, thymomas, or carcinomas, DMSO was found either not to alter or to inhibit TNF‐induced cell death. The latter results are in good agreement with data reported by others who suggested that DMSO could act as a scavenger of TNF‐induced toxic radical formation. The potential correlation in myeloid cells between DMSO‐induced changes in the cells' differentiation status and DMSO‐enhanced TNF‐susceptibility is discussed.J. Leukoc. Biol. 57: 141–151; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.141

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractWe examined the ability of nitric oxide (NO) to stimulate the ADP‐ribosylation of proteins from the mouse macrophage cell line ANA‐1. To demonstrate a specific effect of NO, we used a novel compound named diethylamine dinitric oxide (DEA/NO; l,l‐diethyl‐2‐hydroxy‐2‐nitrosohydrazine, sodium salt; [Et2NN(O)NO]Na), which releases NO in aqueous solution at neutral pH. DEA/NO stimulated the ADP‐ribosylation of at least three cytosolic proteins (Mr= 28,000, 33,000, and 39,000) from ANA‐1 macrophages. The effect of DEA/NO on the ADP‐ribosylation of the predominant target p39 was dose dependent (EC50= 80μM). Moreover, the effect of DEA/NO was attributed specifically to released NO rather than diethylamine or nitrite. Sodium nitroprusside (SNP) also stimulated the ADP‐ribosylation of cytosolic proteins from ANA‐1 mouse macrophages. However, SNP exhibited different time‐ and dose‐dependent effects on the modification of p39. NO synthesized via the activity of interferon‐γ plus lipopolysaccharide‐induced NO synthase also enhanced the ADP‐ribosylation of p39, confirming that the effects of DEA/NO and SNP could be attributed to NO or reactive nitrogen oxide species. Neither pertussis toxin nor cholera toxin stimulated the ADP‐ribosylation of p39; however, cholera toxin stimulated the ADP‐ribosylation of proteins with approximate molecular weights of 28,000 and 33,000. These data suggest that the induced expression of NO synthase in tumoricidal macrophages may be associated with autocrine and paracrine effects of NO that include the ADP‐ribosylation of various proteins. Moreover, these results indicate that DEA/NO and related compounds may be useful as pharmacologic tools for investigating the effects of NO and reactive nitrogen oxide species on macrophages. J.Leukoc. Biol.57: 152–159; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.152

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractTransduction through FcR2/CD23 was analyzed in normal human monocytes using immunoglobulin E (IgE)‐anti‐IgE immune complexes (IgE ICs) and monoclonal antibodies (mAbs) to CD23. Anti‐CD23 mAb and IgE IC triggered a time‐dependent increase in cGMP and cAMP in interleukin‐4–preincubated (CD23+) but not in unstimulated (CD23‐) monocytes. Maximal cGMP and cAMP accumulations were observed 10 and 20 min, respectively, after the onset of CD23 ligation. The increase in cGMP was inhibited withNω‐monomethyl‐l‐arginine (L‐NMMA), which also partially affected cAMP accumulation. Addition of an anti‐CD23 mAb Fab fragment inhibited the IgE IC– and the anti‐CD23 mAb–induced cGMP and cAMP accumulation, confirming the engagement of CD23. In addition, IgE IC and anti‐CD23 mAb induced, at least in some donors, a production of nitrite that was inhibited in the presence of L‐NMMA. Taken together, these findings suggest a possible involvement of the nitric oxide synthase pathway in IgE IC–mediated activation of CD23+monocytes.J. Leukoc. Biol.57: 160–167; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.160

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractMonoclonal antibodies to murine vascular cell adhesion molecule‐1 (VCAM‐1, CD106) revealed not only the expected VCAM‐1 molecule with an apparent molecular weight of 100 kDa, but also a molecule with a smaller size of 46 kDa in stromal cells and stimulated endothelial cells. Peptide mapping suggested the 46 kDa and 100 kDa proteins were closely related. The 46 kDa, but not 100 kDa protein, was cleaved from the cell surface with phosphatidylinositol‐specific phospholipase C (PI‐PLC), showing that the 46 kDa protein was a GPI‐linked molecule. The 46 kDa and 100 kDa isoforms of VCAM‐1 were shown to beN‐glycosylated, have similar kinetics of biosynthesis, and to be partially shed from the cell surface with a slight reduction of size. TNF‐αinduced both isoforms of VCAM‐1 with a similar time course of appearance on the surface of endothelial cells. The relative amounts of the 46 kDa and 100 kDa isoforms depended on the cell type examined. The GPI‐anchored isoform is functionally important, because on a cell on which it was expressed almost as well as the 100 kDa isoform, treatment with PI‐PLC reduced VLA‐4‐dependent conjugate formation.J. Leukoc. Biol.57: 168–173; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.168

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractThe effects of bacterial lipopolysaccharide (LPS) on macrophage gene expression are mediated in part by its ability to induce activation of transcription factor NF‐χB. We compared the ability of LPS‐treated macrophages fromLpsn(LPS‐responsive) C3H/HeN andLpsd(LPS‐hyporesponsive) C3H/HeJ mice to mobilize NF‐χB by electrophoretic mobility shift assays with oligonucleotide probes containing a unique NF‐χB sequence from the promoter of inducible nitric oxide synthase (iNOS). In response to ng/ml concentrations of LPS, this probe bound proteins that appeared rapidly in the nuclei of thioglycollate‐elicited macrophages and bone marrow–derived macrophage cell lines from bothLpsnandLpsdmice. Only in macrophages fromLpsnmice, however, was LPS able to induce iNOS or tumor necrosis factorα.NF‐χB‐containing DNA‐protein complexes fromLpsdmacrophages were formed in lesser amounts than fromLpsnmacrophages but shared the same composition, insofar as they displayed the same electrophoretic mobilities and content of heterodimers of p50/RelA (p65) and p50/c‐rel. Two conclusions emerge from these findings: (1) NF‐χB activity alone is not sufficient for induction of certain LPS‐responsive genes and (2) An LPS‐response pathway involving activation of NF‐χB is preserved inLpsdmice. The inability of cells fromLpsdmice to induce gene expression in response to LPS thus cannot be attributed to inability to activate NF‐χB. J.Leukoc. Biol.57: 174–179; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.174

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractcDNA cloning revealed the presence of two related but distinct types of human interleukin‐8 (IL‐8) receptors, type I (type A) and type II (type B). By immunizing rabbits with glutathione‐S‐transferase fused with the NH2‐terminal domain of each type of IL‐8 receptor, we prepared polyclonal antibodies that specifically recognized the NH2‐terminal domain of each type of IL‐8 receptor. Immunofluorescence analysis of human peripheral blood leukocytes demonstrated that mature granulocytes except eosinophils express both types of IL‐8 receptors. A majority of monocytes and CD16+natural killer (NK) cells in peripheral blood were stained with both antibodies, whereas CD3+T or CD20+B lymphocytes in peripheral blood or CD34+cells in cord blood were not stained with either antibody. These results suggest that both types of human IL‐8 receptors were coordinately and selectively expressed in mature granulocytes, monocytes, and CD16+NK cells.J. Leukoc. Biol.57: 180–187; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.180

出版商:Wiley    

年代:1995

数据来源: WILEY

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.i

出版商:Wiley    

年代:1995

数据来源: WILEY