| 1. |
- Gannedahl, G, et al.
(author)
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Role of antibody synthesis and complement activation in concordant xenograft retransplantation.
- 1994
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In: Transplantation. - 0041-1337 .- 1534-6080. ; 58:3, s. 337-344
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Journal article (peer-reviewed)abstract
- A mouse-to-rat heart retransplantation model was used to study the effects of complement depletion and antibody production with regard to graft survival and anti-donor antibody specificity. Retransplantation was performed 3 weeks after the first transplantation in the presence of absence of 15-deoxyspergualin (DSG) immunosuppression. Untreated animals rejected their first graft after 3 days and retransplantation resulted in a hyperacute rejection within 2 min. A low titer of preformed anti-mouse lymphocytotoxic antibodies of the IgM subclass was found in serum collected from the unoperated rat. The rejection gave rise to a synthesis of IgG antidonor antibodies reacting with both graft endothelium and sarcolemma. Immunofluorescent staining of the rejected first heart graft showed moderate IgM and IgG antibody deposits on the graft vascular endothelium, while only IgG was found in the second graft. There was no C3 deposition found in the first mouse graft, as was the case in the second mouse graft. Anti-mouse antibodies cross-reacted with hamster antigens and a hyperacute rejection of a hamster heart graft occurred in a mouse-sensitized rat. Immunofluorescent staining revealed that the antibodies did not bind to hamster heart endothelium, as was expected, but, instead, to graft sarcolemma. DSG treatment prolonged the survival of the first graft by a median of 8 days. Continuous treatment until retransplantation resulted in a prolongation to 30 (20-127) min of the survival of the second graft and no increase in antibody titers against mouse antigens was observed. However, immunofluorescent staining revealed a weak binding of anti-mouse antibodies of the IgM subclass in the rejected mouse heart graft. Additional complement depletion with cobra venom factor in DSG-treated animals resulted in a prolongation of the median graft survival to 48 hr (6-96). No sign or minimal signs of antibody deposition were found in these grafts, but histology revealed massive mononuclear infiltration. In conclusion, xenograft transplantation in a concordant situation results in a shift of antidonor antibody Ig synthesis from IgM to IgG. If daily DSG treatment is administered from the day of transplantation, this reduces the synthesis of antidonor antibodies, and if complement is also depleted, the survival of the second graft is prolonged. The significance of the mononuclear infiltration remains to be established.
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| 2. |
- Wanders, A., et al.
(author)
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Evidence that LS-2616 (linomide) causes acute rejection of rat allografts protected by cyclosporine but not of long-term surviving allografts
- 1991
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In: Transplantation. - 0041-1337 .- 1534-6080. ; 52:2, s. 234-8
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Journal article (peer-reviewed)abstract
- The immunomodulator LS-2616 (Linomide) induces rejection of cyclosporine-protected rat cardiac allografts. The aim of this study was to characterize this rejection in the presence of CsA and to test LS-2616 in other models of permanent graft acceptance in the rat. PVG rat hearts were transplanted heterotopically to Wistar/Kyoto (Wi/Ky) rat recipients on day 0. The recipients were treated orally on days 0-9 with CsA (10-40 mg/kg) and/or with LS-2616 (2.5-160 mg/kg) starting at different times (day -7 -+5) until the day of complete rejection. The addition of LS-2616 (day -1--stop) to CsA (10 mg/kg) resulted in a dose-dependent antagonism of the immunosuppressive effect of CsA with daily doses of 2.5-160 mg/kg. Furthermore, the results were similar, irrespective of whether LS-2616 treatment (160 mg/kg) was started on day -7, -1, +1, +3, or +5. LS-2616 (160 mg/kg) pretreatment of the recipient for 7 days before transplantation was considerably less effective. CsA (20 mg/kg) for 14 days after a PVG to DA transplantation resulted in permanent graft survival. This was not abrogated by LS-2616. Neither was rejection induced in long-term surviving grafts of RT1.C incompatible Lewis recipients. Our data suggest that LS-2616 activates already stimulated and sensitized T cells that are otherwise controlled by CsA.
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| 3. |
- Riesbeck, Kristian, et al.
(author)
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Evidence that the antibiotic ciprofloxacin counteracts cyclosporine‐dependent suppression of cytokine production
- 1994
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In: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 57:2, s. 267-272
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Journal article (peer-reviewed)abstract
- The fluoroquinolone antibiotic ciprofloxacin (cipro) has been reported to upregulate interleukin 2 and interferon-γ production in lectin-stimulated lymphocytes. The aim of this study was to elucidate whether cipro and the immunosuppressive agent CsA have antagonistic action on cytokine synthesis. Accumulation of IL-2 and IFN-γ protein and mRNA were analyzed in polyclonally (PHA or Con A) or alloantigen-stimulated human peripheral blood lymphocytes. CsA added simultaneously with PHA partially blocked cytokine synthesis. The present study also shows that cipro supplemented with CsA and PHA resulted in significant higher concentrations of IL-2 (up to 60 times) and IFN-γ (4.3 times) as compared with PHA and CsA alone. Similar results were obtained with primary mixed lymphocyte reactions. In parallel, a greater amount of IL-2 and IFN-γ mRNA was observed in lymphocytes incubated with both cipro and CsA as compared with CsA alone. Our results reveal that CsA-dependent inhibition of both IL-2 and IFN-γ expression is counteracted by high concentrations of cipro. These findings may be of importance in clinical transplantation.
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| 4. |
- Rydberg, Lennart, 1944, et al.
(author)
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ABO-incompatible kidney transplantation (A2 to O). Qualitative and semiquantitative studies of the humoral immune response against different blood group A antigens.
- 1990
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In: Transplantation. - 0041-1337. ; 49:5, s. 954-60
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Journal article (peer-reviewed)abstract
- The humoral immune response against blood group A antigens with different core saccharide structures has been investigated in four blood group O recipients transplanted with kidneys from two blood group A2 donors. Radioimmunoassay and thin-layer chromatogram binding assay studies showed that different individuals responded differently to the same antigenic stimulus. Antibodies were produced in the recipient that bound to the terminal trisaccharide of the blood group A antigens. In some cases antibodies that bound to a larger antigen epitope, including the fourth and fifth sugar in the polysaccharide core chain, also occurred. Immunoglobulin class-specific, as well as subclass specific, responses were seen. The antibody response in the blood group O recipients receiving an A2 graft seem to be dependent on the antigenic expression in the transplanted kidney. In view of the recent findings of individuality of A antigen expression in kidneys within the A1 and A2 subgroups, an extended typing of A2 donors may be important. The humoral immune response in the recipient may also be dependent on earlier contacts with ABO incompatible pregnancies, vaccinations, or infections. A possible correlation between pre- and posttransplant findings was noted in one case and deserves further notice.
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| 5. |
- Rønholm, Ebbe, 1960, et al.
(author)
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Complement system activation during orthotopic liver transplantation in man. Indications of peroperative complement system activation in the gut.
- 1994
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In: Transplantation. - 0041-1337. ; 57:11, s. 1594-7
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Journal article (peer-reviewed)abstract
- Sixteen patients with acute and chronic liver disease undergoing OLT were studied regarding the role of the liver and the gut in complement activation. Also, the relation between complement activation and clinical manifestations during the liver transplantation reperfusion period was investigated. Blood samples for measurement of complement anaphylatoxin C3a (C3a), complement anaphylatoxin C5a (C5a), and terminal C5b-9 complement complex (TCC) were taken simultaneously from the central venous catheter and the radial arterial line before starting the operative procedure, 1 min before declamping, and 1-2 min, 5 min, 30 min and 6-12 hr after declamping. Simultaneous blood sampling from the radial arterial line, central venous catheter, portal vein, and hepatic vein was performed 1-2 min and 5 min after completed unclamping. Elevated plasma levels of C3a and TCC were found upon reperfusion, while C5a levels remained unchanged throughout the operation compared with the preoperative levels. The levels of C3a in the portal vein were higher compared with the levels in the simultaneously obtained samples from the radial artery. The results indicate complement cascade activation located to the gut during the reperfusion phase of OLT. Seventy-five percent of the patient studied suffered from the postreperfusion syndrome, indicated by profound hypotension upon reperfusion of the transplanted liver. There was a significant correlation between high concentration of C3a anaphylatoxin and development of profound hypotension.
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