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R B Landewé A M Miltenburg F C Breedveld M R Daha B A Dijkmans 《The Journal of rheumatology》1992,19(9):1353-1357
OBJECTIVE: To investigate synergistic interaction between cyclosporine (Cy) and chloroquine (Chl) in an in vitro system, with regard to interferon-gamma (IFN) production by OKT3 activated T cell clones. METHODS. CD4+ and CD8+ T cell clones, derived from synovial tissue of a patient with rheumatoid arthritis (RA) were activated with plastic coated OKT3 monoclonal antibody in the presence or absence of various concentrations of Cy, Chl and their combinations. After 24 h of incubation the supernatants were assayed for IFN by ELISA. RESULTS. Cy as well as Chl were able to completely inhibit in a concentration dependent fashion the IFN production by CD4+ and CD8+ T cell clones. Combinations of Cy and Chl, which in themselves give minor inhibition of IFN production, were able to inhibit in a synergistically enhanced fashion the production of IFN by these clones. The synergy was formally proven by the construction of isoboles. This synergy was most pronounced when drug concentrations were used which individually gave minor inhibition of IFN production. CONCLUSION. We conclude that the results of our in vitro experiments may give rise to further investigation of the promising combination of Cy and Chl in the treatment of RA. 相似文献
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Kupffer cell depletion in vivo results in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells. 总被引:2,自引:1,他引:1
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W M Bogers R K Stad D J Janssen N van Rooijen L A van Es M R Daha 《Clinical and experimental immunology》1991,86(2):328-333
In the present study we have investigated the clearance kinetics and tissue distribution of monomeric (m) IgG and soluble aggregates of IgG (AIgG) and immune complexes (IC) in normal and Kupffer cell (KC) depleted rats. In normal rats, clearance of mIgG occurred in a biphasic manner with a first half-life (T1/2) (T1) of 36.3 +/- 6.3 min and a second T1/2 (T2) of 168.4 +/- 4.7 min. AIgG composed of 20-27 IgG molecules per aggregate were cleared significantly faster than mIgG with a T1 of 2.5 +/- 0.1 min and a T2 of 32.5 +/- 5.6 min. KC depletion did not have a significant effect on the clearance rate of mIgG (T1: 33.4 +/- 8.9 min; T2; 159.5 +/- 12.5 min), while clearance of AIgG was delayed significantly with T1 4.8 +/- 0.7 min and T2 41.2 +/- 3.2 min. Eight minutes after injection, 77% of AIgG was found in the liver in normal rats while 62% was found in the liver of KC-depleted rats. Double immunofluorescence studies indicated that AIgG in the liver was associated with KC and endothelial cells (EC) in normal rats. In KC-depleted rats, AIgG was strongly associated with EC. A similar staining pattern was observed when IgG-immune IC were administered. The clearance of AIgG in KC-depleted rats was inhibited fully by pre-administration of high concentrations of IgG but not by pretreatment with IgA. asialofetuin (ASFe) or ovalbumin (OVA). Aggregated F(ab')2IgG was cleared with a comparable rate to mIgG from the circulation, again suggesting Fc gamma receptor-mediated elimination of AIgG by EC. There was a reduced degradation of AIgG in rats depleted of KC as compared with normal rats. These data suggest binding and degradation of AIgG by EC in vivo. 相似文献
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Endothelial cell lysis induced by lymphokine-activated human peripheral blood mononuclear cells 总被引:5,自引:0,他引:5
A M Miltenburg M E Meijer-Paape M R Daha L C Paul 《European journal of immunology》1987,17(9):1383-1386
In vitro exposure of human peripheral blood mononuclear cells (PBMC) to interleukin 2 results in the generation of lymphokine-activated killer (LAK) cells. Such LAK cells exhibit cytotoxicity against a spectrum of tumor target cell lines whereas they apparently do not affect normal tissues. In this report we show that PBMC that have been activated with T cell growth factor lyse trypsinized human umbilical cord venous endothelial cells as well as endothelial cell monolayers in a dose-dependent manner. Microscopic analysis showed that during the 4-h incubation period cell clumps containing detached endothelial cells and LAK cells were formed. When these clumps were evaluated with trypan blue the endothelial cells stained positive whereas LAK cells excluded the dye. No lysis occurred when fresh PBMC were added to target endothelial cells. The endothelial cell kill could not be blocked with an anti-LFA-1 antibody nor with intact OKT3 or F(ab')2 fragments of WT32. We conclude that lymphokine-activated PBMC exhibit cell-mediated endothelial cell detachment and lysis. 相似文献
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D. van Riessen M. R. Daha T. J. M. Smeets F. C. Breedveld 《Rheumatology international》1992,12(1):1-5
Summary It has been suggested that the reduced resistance of patients with rheumatoid arthritis (RA) to bacterial joint infections may be due in part to polymorphonuclear cell (PMN) function. To obtain further insight into the mechanis that contribute to the increased susceptiblity of RA patients to such infections we investigated the influence of different solid surfaces on the ingestion of various bacterial strains by PMN. Both in the presence and absence of serum, phagocytosis of bacteria by PMN was significantly lower on monolayers of synovial fibroblasts as compared to monolayers of endothelial cells and embryonic fibroblasts. It could be shown that the relative influence of the solid surfac on the results of the phagocytosis assay increased when decreasing concentrations of purified IgG were used. The results of this study sugpurified IgG were used. The results of this study suggested that the effect of synovial fibroblasts on PMB may lead to reduced clearance of bacteria from the joint. 相似文献
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S. van Ruth† EBL van Dorst‡ MR Canninga-van Dijk§ MS de Bruin-Weller† 《Journal of the European Academy of Dermatology and Venereology》2007,21(5):678-680
Cutaneous metastasis of vaginal carcinoma is extremely rare. So far, the total number of reported skin metastasis of vaginal carcinoma is only one. We present another case with an unusual manifestation of vagina carcinoma metastasis: skin metastasis presenting as a leg ulcer on the lower leg. 相似文献
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Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells. 总被引:3,自引:1,他引:2
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W M Bogers R K Stad D J Janssen F A Prins N van Rooijen L A van Es M R Daha 《Clinical and experimental immunology》1991,85(1):128-136
We investigated the clearance kinetics and tissue distribution of different sized IgA in normal and macrophage-depleted rats. Rats were injected iv with liposomes containing dichloromethylene diphosphonate (DMDP). DMDP treatment resulted in complete depletion of liver macrophages 24-48 h after administration. Normal and macrophage depleted rats were injected intravenously with monomeric, dimeric, polymeric or aggregated polymeric IgA (AIgA) and assessed for blood clearance and tissue distribution. In normal rats, clearance of IgA was size dependent, i.e. a faster clearance with increasing size. No differences in clearance kinetics were observed of the different sized IgA between normal and DMDP-treated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AIgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-treated rats. Immunofluorescence studies on liver biopsies indicated that AIgA was associated with Kupffer cells in normal rats. Electron microscopical studies revealed that the AIgA was internalized and located in vesicles in Kupffer cells. In DMDP-treated rats the AIgA was associated with endothelial cells and electron microscopy studies showed that this AIgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AIgA in situations where Kupffer cells are absent, and that these cells may play an important role in the handling of AIgA and IgA-immune complexes. 相似文献
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Characterization of anti-endothelial cell antibodies in systemic lupus erythematosus (SLE). 总被引:4,自引:2,他引:2
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J M van der Zee C E Siegert T A de Vreede M R Daha F C Breedveld 《Clinical and experimental immunology》1991,84(2):238-244
IgG anti-endothelial antibodies (AEA), as measured by ELISA or immunoblotting technique could be detected in serum samples of 56 out of 64 patients with SLE (88%) and mainly occurred in monomeric form. AEA were not cell specific, because the binding reactivity was absorbed partially by both fibroblasts and peripheral blood mononuclear cells. No correlation was found between the presence of AEA and anti-nuclear antibodies. Immunoblotting revealed reactivity of AEA against endothelial antigens ranging in size from 15 to 200 kD. AEA titres were significantly higher in patients with joint or skin abnormalities, compared with patients without these abnormalities. A significant correlation was found between nephritis in SLE and the presence of AEA reactivity against endothelial membrane antigens of 38, 41 and 150 kD. These data show that the pattern of AEA reactivity in serum of SLE patients is heterogeneous, and suggest that AEA against a limited number of antigens may be involved in the pathogenesis of nephritis in SLE. 相似文献