High-Dose Stabilized Chlorite Matrix WF10 Prolongs Cardiac Xenograft Survival in the Hamster-to-Rat Model without Inducing Ultrastructural or Biochemical Signs of Cardiotoxicity

Hansen, Alastair; Kemp, K.; Kemp, E; Bouchelouche, Kirsten; Bouchelouche, Pierre; Dieperink, Hans; Horn, Thomas; Larsen, Svend

doi:10.1034/j.1600-0773.2001.d01-141.x

Cited by 8 publications

(7 citation statements)

References 6 publications

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“…Many diseases are accompanied by long-lasting chronic inflammations with disturbed processes of immune regulation. In a number of cases, the application of WF10 improved the disease state of these patients [10][11][12][13][25][26][27][28]. Thus, our data about the inhibition of activation processes in monocytes and macrophages by WF10 coincide well with the results about clinical application of WF10.…”

Section: Discussionsupporting

confidence: 77%

“…In macrophages, WF10 is known to decrease the expression of TNFα [11], to diminish the antigen presentation that diminishes Tcell proliferation [21,22], and to enhance the interaction with fibroblasts [11]. WF10 inactivates AIDS viruses [10,23], enhances the cytotoxicity of natural killer cells [24], and prolongs cardiac graft survival in a rodent xenotransplantation model [25]. Further, the application of WF10 attenuates the disease state in radiation-associated tissue damage [12,26,27], in diabetic foot ulcera [13], and in wound healing [28,29].…”

Section: Discussionmentioning

confidence: 99%

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Effects of WF10 on Glycosaminoglycan Sulphation in Proinflammatory Monocytes and Macrophages

Schönberg¹,

Schlorke²,

Arnhold³

2016

Flow Cytometry - Select Topics

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The chlorite-based drug solution WF has been successfully applied to dampen strong inflammatory disease states and to improve wound healing processes. However, the molecular mechanisms of this drug are not well understood. This study is directed to investigate how WF and its components affect the expression of surface markers and sulphated proteoglycans and glycosaminoglycans in proinflammatorystimulated monocytes and macrophages.Human blood-derived macrophages were cultivated from monocytes in the presence of U/ml granulocyte-macrophage colony-stimulating factor and activated by a mixture of ng/ml lipopolysaccharide LPS and ng/ml interferon γ IFNγ . These cells were identified and characterised by their specific cell-surface receptors CD , CD , CD , CD , CD , and CD using flow cytometry approaches. The sulphation level of proteoglycans and glycosaminoglycans was assessed by the Blyscan™ dye-binding assay. The expression of the surface marker CD , a proteoglycan with sulphated glycosaminoglycan side chains, was followed by antibodies against CD . The binding of fluorescence-labelled hyaluronan to CD was also investigated by flow cytometry. All analyses were performed after incubation of monocytes and macrophages with WF or with its main components chlorite and chlorate.The drug substance WF inhibited the activation of LPS/IFNγ-stimulated human monocyte-derived macrophages. Among them are the diminished expression of proinflammatory surface markers, the inhibition of the expression of the hyaluronan receptor CD , and the binding of hyaluronan to CD . Further, the overall amount of sulphated proteoglycans and glycosaminoglycans was down-regulated by WF . These in vitro experiments indicate that WF is able to inhibit the proinflammatory activation of macrophages. The results suggested that chlorite is the active principle in WF as chlorite caused principally the same changes in targets as WF . The WF component chlorate inhibited only the overall sulphation level of proteoglycans and glycosaminoglycans and the binding of hyaluronan to CD .

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Effects of WF10 on Glycosaminoglycan Sulphation in Proinflammatory Monocytes and Macrophages

Schönberg¹,

Schlorke²,

Arnhold³

2016

Flow Cytometry - Select Topics

View full text Add to dashboard Cite

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“…The heart transplantations were performed as previously described (7). Briefly, the donor GT‐Ko mice were anesthetized with fentanyl/fluanisone (1 mg/0.002 mg per 100 g body weight) and diazepam (0.5 mg per 100 g body weight).…”

Section: Methodsmentioning

confidence: 99%

“…For pain relief donors were given pentobarbital and recipients were given a combination of hypnorm, stesolid and temgesic. The experiment ended as the transplanted heart stopped beating (7, 8).…”

Section: Methodsmentioning

confidence: 99%

The resistance of delayed xenograft rejection to α(1,3)‐galactosyltransferase gene inactivation and CD4 depletion in a mouse‐to‐rat model

Hansen

Kirkeby²,

Aasted³

et al. 2003

APMIS

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Critical to the prevention of xenograft loss is the prevention of delayed xenograft rejection (DXR), due to its resistance to conventional immunosuppression. The role of the carbohydrate galactose-alpha1,3-galactose (alpha1,3Gal) has been a matter of great debate and it has been proposed that the reaction between alpha1,3Gal epitopes on donor endothelial cells and recipient anti-alpha1,3Gal antibodies (Abs) may damage the graft during DXR. Recipient anti-alpha1,3Gal Abs are produced by CD4-dependent B cells. To test the above-mentioned hypothesis, hearts from alpha1,3Gal-free mice (GT-Ko mice), generated by alpha1,3-galacto-syltransferase gene disruption, were transplanted to anti-alpha1,3Gal antibody-free Lew/Mol rats. This model consists of an alpha1,3Gal/alpha1,3Gal-antibody-free environment, eliminating a possible influence of this specific system on DXR. A subgroup of recipients were furthermore CD4 depleted in order to inhibit CD4-dependent B-cell antibody production. Rejected hearts were evaluated by light- and immunofluorescence microscopy. Treatment effects on recipient T-cell subsets and cytokine expression were analyzed by flow cytometry, while antibody production was measured by ELISA. All recipients developed DXR with no differences among the groups. DXR was related to thrombosis with IgG and IgM desposition in vessel walls, as well as macrophage and granulocyte accumulation in the myocardium. No complement C3, CD4 cells or NK cells were found. Flow cytometric analysis confirmed peripheral blood CD4 depletion and IFN-gamma suppression in CD4 Ab-treated recipients. Finally, ELISA showed that specific anti-alpha1,3Gal Ab production was absent. However, Ab(s) against an unidentified Galalpha 1 were found among recipients. In our model, DXR is resistant to alpha1,3-galactosyltransferase gene inactivation and CD4 depletion. However, other Galalpha 1 epitopes and antibodies may play a role during DXR. Further studies are needed to elucidate the precise pathways leading to DXR.

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“…All the described alterations were in accordance with the terminal phase of rejection. Wf10 alone without transplantation did not induce these changes (Hansen et al 2001).…”

Section: Overview Of the Transplanted Animals Included In This Studymentioning

confidence: 98%

Immunosuppression in Xenotransplantation with Wf10

Kemp

Dieperink

Hansen

et al. 2002

Pharmacology & Toxicology

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High-Dose Stabilized Chlorite Matrix WF10 Prolongs Cardiac Xenograft Survival in the Hamster-to-Rat Model without Inducing Ultrastructural or Biochemical Signs of Cardiotoxicity

Cited by 8 publications

References 6 publications

Effects of WF10 on Glycosaminoglycan Sulphation in Proinflammatory Monocytes and Macrophages

Effects of WF10 on Glycosaminoglycan Sulphation in Proinflammatory Monocytes and Macrophages

The resistance of delayed xenograft rejection to α(1,3)‐galactosyltransferase gene inactivation and CD4 depletion in a mouse‐to‐rat model

Immunosuppression in Xenotransplantation with Wf10

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