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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 36 (1992), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In this study, the mechanisms underlying stimulation of T-cell proliferation by human blood dendritic cells (BDC) and their differentiation have been defined with a panel of monoclonal antibodies (MoAbs)- It was found that the MoAbs against LFA-I (CDlla), CD11c. LFA-3 (CD58), ICAM-1 (CD54) or HLA-DR could significantly suppress T-cell proliferation in an allogeneic mixed lymphocyte reaction (P〈0.05), while being unable to inhibit clustering of BDC with T cells. Addition of anti-CD18 or CD45 MoAbs increased the size of clusters after 18 h of culture, but had no effect on the proliferation of T cells (P〈0.05). The suppressive effect of the MoAbs may be viewed not as an inhibition of contact between BDC and T cells, but rather as a blocking of co-stimulatory signals for T-cell activation, which are mediated by interaction of the adhesion molecules. After depleting the BDC preparations of monocytes. we used a double staining in FACS analysis to demonstrate that BDC do not express specific T (CD3), B (CD20 and CD2l)and myeloid cell markers (CDl1b, CDl3 and CD14), but abundant class II antigens. This pattern remained unaltered after 8 days of culture in the presence of 100 U/ml GM-CSF, although a threefold increase of HLA-DQ and ICAM-1 molecules on the cultured cells was observed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Cyclosporine ; Calcium ; Vascular smooth muscle ; Mesangial cells ; Atrial natriuretic peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunosuppressive therapy with cyclosporine A (CyA) may be associated with severe side effects such as nephrotoxicity and arterial hypertension. The partial reversibility of these effects suggests that they are at least in part functional. The present study examined the effects of CyA on cellular signaling in vascular smooth muscle cells and in glomerular mesangial cells and the interactions with the endogenous vasodilator atrial natriuretic peptide (ANP). Intracellular free calcium concentrations ([Ca2+]i) were measured using Fura-2. 45Ca2+ was used to measure Ca2+ efflux and cellular Ca2+ influx. In the presence of cyclosporine (10 μg/ml), the Ca2+-mobilizing effects of angiotensin II (10−8 M) in smooth muscle cells and of arginine vasopressin (AVP) in mesangial cells were significantly enhanced. CyA significantly stimulated cellular Ca2+ uptake in both cell types. ANP blocked the Ca2+ mobilization by angiotensin II and AVP and also completely inhibited the potentiating effect of CyA on angiotensin II- and AVP-induced Ca2+ mobilization. ANP also completely blocked the CyA-stimulated Ca2+ uptake. These findings suggest that CyA stimulates transmembrane Ca2+ influx, thereby increasing vasopressor-sensitive intracellular Ca2+ stores and augmenting vasopressor-induced Ca2+ mobilization. This cellular effect of CyA in vitro was markedly diminished by ANP. The effects of CyA on intracellular signaling may directly enhance the contractile response of smooth muscle and the glomerular mesangium to vasopressor stimuli and may also contribute to other disturbances of cell metabolism associated with CyA.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Cyclosporine ; Calcium ; Na-KATPase ; Vascular smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of cyclosporine A in enhancing vasconstrictor-induced calcium (Ca2+) mobilization in vascular smooth muscle cells may contribute to important side effects in cyclosporine therapy such as hypertension and nephrotoxicity. As we have previously shown, cyclosporine A stimulates transmembrane Ca2+ influx. Since Ca2+ efflux was not affected by cyclosporine A, we concluded that cyclosporine augments angiotensin II induced Ca2+ mobilization in vascular smooth muscle cells by an increased amount of Ca2+ in angiotensin II sensitive intracellular Ca2+ stores. The present study was therefore designed to examine the effect of cyclosporine A on cellular calcium content and on membrane calcium transport mechanisms. An important mechanism of Ca2+ extrusion from the cell is the Na-Ca exchanger. Its activity is closely related with that of the Na-ATPase. By increasing cellular sodium concentration the blockade of Na-ATPase would in turn activate cellular calcium uptake bx the Na-Ca exchanger. Therefore, we hypothesized that cyclosporine A might exert its effects in the same manner as a circulating Na-ATPase inhibitor. Total cell calcium was measured by atomic absorption and activity of Na-ATPase was estimated by an assay measuring phosphate production. Preincubation of the cells with cyclosporine (10 μg/ml) for 15 min increased total cell calcium from 31.4 ± 5.0 to 46.5 ± 5.3 nmol/mg protein (P 〈 0.05). Activity of Na-ATPase was not affected by cyclosporine A (3.9 ± 0.2 vs. 4.3 ± 0.2 μol Pi h−1 mg−1 protein). Therefore, cyclosporine A induced Ca2+ influx is not mediated by an inhibition of the Na-ATPase. Cyclosporine-stimulated accumulation of cellular calcium may be mediated, for example, by opening of calcium channels in the plasma membrane. Increased Ca2+ mobilization in the presence of cyclosporine A may be due to an increased amount of Ca2+ avaible from intracellular Ca2+ stores. These results are of substantial significance for understanding the pathophysiological mechanisms of cyclosporine A induced vasoconstriction.
    Type of Medium: Electronic Resource
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