| 1. |
- Larsson, R, et al.
(författare)
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Inhibition of complement activation by soluble recombinant CR1 under conditions resembling those in a cardiopulmonary circuit : reduced up-regulation of CD11b and complete abrogation of binding of PMNs to the biomaterial surface.
- 1997
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Ingår i: Immunopharmacology. - 0162-3109 .- 1879-047X. ; 38:1-2, s. 119-127
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Tidskriftsartikel (refereegranskat)abstract
- The influence of soluble recombinant CR1 (sCR1) on complement activation, and its indirect effects on the coagulation system and cellular responses were assessed in two models for the study of blood/surface and blood/air interactions, as are encountered in e.g. cardiopulmonary bypass circuits. The concentrations of C3a and sC5b-9 and the amount of bound C3/C3 fragments were analyzed as indicators of complement activation. Thrombin-antithrombin complexes, the platelet count, surface-ATP, beta-thromboglobulin, and the expression of CD11b on leukocytes were the parameters analyzed to reflect coagulation and cellular responses. In addition, immunochemical analyses of the phenotypes of surface-bound leukocytes and platelets were performed. Recombinant sCR1, at doses ranging between 0.1-0.25 mg/ml, was found to completely inhibit the generation of sC5b-9, and of C3a by two thirds; the binding of C3 and/or C3 fragments to the surface was almost entirely abolished. As a result of the inhibition of complement activation, the expression of CD11b on PMNs, and the binding of these cells to the biomaterial surface was almost completely lost. In contrast, the thrombin-antithrombin complexes, the platelet count, and the adherence of platelets to the surface, as reflected by the ATP binding and the release of beta-thromboglobulin, were not affected. These data show that complement activation, in association with extra-corporeal treatment, causes activation and binding of PMNs to the biomaterial and that these effects can be completely abolished by the addition of soluble recombinant sCR1.
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| 2. |
- Riesbeck, Kristian, et al.
(författare)
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Increased interleukin 2 transcription in murine lymphocytes by ciprofloxacin
- 1994
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Ingår i: Immunopharmacology. - : Elsevier BV. - 0162-3109. ; 27:2, s. 155-164
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Tidskriftsartikel (refereegranskat)abstract
- The fluoroquinolone antibiotic, ciprofloxacin (cipro), induces hyperproduction of interleukin 2 (IL-2) and interferon-γ (IFN-γ) in stimulated human peripheral blood lymphocytes. In this investigation an enhanced and prolonged IL-2 and IL-2 mRNA response was also detected in both stimulated (T cell mitogens or alloantigens) murine splenocytes and in the stimulated murine T cell line EL-4 in the presence of ciprofloxacin (5-80 μg/ml) as compared to control cells without antibiotics. However, in contrast to human lymphocytes, IFN-γ production was inhibited and IFN-γ mRNA levels were unaffected at 24 h and only slightly upregulated at 48 and 72 h of culture in murine splenocytes incubated with cipro (20 μg/ml). EL-4 cells were transfected with a plasmid containing the IL-2 promoter and enhancer region linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Analysis of CAT activity revealed that cipro enhanced IL-2 gene induction. In addition, EL-4 cells incubated with ciprofloxacin showed an early peak and more activated nuclear factor of activated T cells (NFAT-1) as compared to control cells without antibiotics. Cipro did not affect the nuclear transcription factors AP-1 or NFIL-2A. Taken together, cipro inhibited IFN-γ synthesis, but enhanced IL-2 production in murine lymphocytes by means of influencing NFAT-1 and causing an increased IL-2 transcription.
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