O Gottschalk

Publications (5)12.59 Total impact

• Article: Selective inhibition of platelets by the GPIIb/IIIa receptor antagonist Tirofiban reduces leukocyte-endothelial cell interaction in murine antigen-induced arthritis.

  M Schmitt-Sody, P Metz, O Gottschalk, S Zysk, C Birkenmaier, M Goebl, C von Schulze Pellengahr, A Veihelmann, V Jansson
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  ABSTRACT: Inflammation is associated with the invasion of leukocytes into affected tissues and with the up-regulation of platelet activation and adhesion. Assuming that leukocyte accumulation is linked to platelet aggregation, the aim of our study was to examine the effects of selective platelet inhibition by the glycoprotein (GP) IIb/IIIa receptor antagonist Tirofiban on the leukocyte-endothelial cell interaction. We used the model of antigen-induced arthritis (AiA) to induce inflammatory changes in the synovial microcirculation. Ex vivo labelled platelets and in vivo fluorescence-labelled leukocytes were visualized by intravital microscopy (IVM). C57/Bl6 mice were allocated to four groups; two control groups with saline or Tirofiban and two groups with AiA that also received either saline or Tirofiban (0.5 microg/g BW) intravenously. There was no significant change in platelet- or leukocyte- endothelial cell interaction in the endothelium in healthy control animals. In contrast, after selective inhibition of platelets, the platelet- and leukocyte-endothelial cell interaction was significantly reduced in arthritic mice and reached the level of the healthy control groups. Selective platelet inhibition by Tirofiban resulted in reduced leukocyte-endothelial cell interactions in AiA. Consequently, platelets contribute to leukocyte adhesion in AiA via GPIIb/IIIa and therefore platelet inhibition could become an additional therapy option in chronic arthritic disease.
  Inflammation Research 11/2007; 56(10):414-20. · 2.11 Impact Factor
• Article: Platelet P-selectin is significantly involved in leukocyte-endothelial cell interaction in murine antigen-induced arthritis.

  M Schmitt-Sody, P Metz, O Gottschalk, C Birkenmaier, S Zysk, A Veihelmann, V Jansson
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  ABSTRACT: There is growing evidence that platelets play an important role in the development and maintenance of rheumatoid arthritis. Activation and adherence of platelets in the synovial microcirculation might be in part responsible for endothelial damage and activation of leukocytes. Recent findings show a direct influence of P-selectin on platelet- and leukocyte-endothelial cell interaction in mice with Antigen-induced Arthritis (AiA). P-selectin is only expressed by platelets and endothelial cells, not by leukocytes. Therefore, the aim of the present study was to investigate the differential influence of platelet and endothelial P-selectin on the extent of inflammation in AiA. AiA was induced in wild-type mice and in P-selectin-deficient mice from the same genetic background (four groups: each n = 7). Intravital fluorescence microscopy (IVM) was used to visualize platelets and leukocytes in the synovial microcirculation at day 8 after AiA. Platelets from either strain were fluorescence-labelled ex vivo and transferred into either strain. We were able to demonstrate a significant decrease of platelet- and leukocyte-endothelial cell interaction in P-selectin-deficient mice with AiA in comparison to wild-type mice with AiA. When wild-type platelets were donated into P-selectin-deficient AiA recipients, the leukocyte-endothelial cell interaction was significantly increased compared to the group consisting of P-selectin-deficient recipient and donor mice. These are the first in vivo results showing that the P-selectin stored in platelets is at least partly responsible for the leukocyte-endothelial cell interaction and the resulting tissue damage in AiA. In the future, a suppression of platelet P-selectin could potentially become a treatment option for reducing the effects of rheumatoid arthritis.
  Platelets 09/2007; 18(5):365-72. · 1.85 Impact Factor
• Article: Endothelial iNOS versus platelet iNOS: responsibility for the platelet/leukocyte endothelial cell interaction in murine antigen induced arthritis in vivo.

  M Schmitt-Sody, O Gottschalk, P Metz, S Zysk, J Hausdorf, C von Schulze Pellengahr, A Veihelmann, V Jansson
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  ABSTRACT: Since an increase of platelet-endothelial cell interactions has been observed in mice with Antigen- induced-Arthritis (AiA) as well as an increase of NO expression, the aim of our study was to investigate in vivo the influence of NO, especially the platelet and endothelial inducible NO Synthase, on the platelet- and leukocyte endothelial cell interaction. C57/Bl6 mice and iNOS deficient mice were disposed in 6 groups (each=7). After induction of AiA, rolling and adherent fluorescence labelled platelets and leukocytes were investigated by intravital microscopy (IVM) on day 8 after AiA. Rank SUM Test and ANOVA on ranks have been performed regarding the data. All arthritic mice presented an increase in platelet and leukocyte interaction with the endothelium compared to control groups. The arthritic iNOS deficient mice showed a more intense interaction of platelets and leukocytes with the endothelium in comparison with the wild-type arthritic mice. The group using arthritic wild-type recipient and iNOS deficient donor mice showed an increase in cell-interactions, leading to an endothelial effect, compared to the group using iNOS deficient arthritic recipient and wild-type donor mice. The IVM data lead to an anti-inflammatory effect of NO, since NO followed an increase in platelet- and leukocyte- endothelial cell interaction in iNOS deficient mice with AiA. In addition, we have shown for the first time in vivo that platelet NO produced by iNOS seems to have a minor influence on the leukocyte induced tissue damage in contrast to endothelial iNOS. Therefore, selective platelet inhibition would not interfere with the protective effect of NO.
  Inflammation Research 07/2007; 56(6):262-8. · 2.11 Impact Factor
• Article: Platelet-endothelial cell interactions in murine antigen-induced arthritis.

  M Schmitt-Sody, A Klose, O Gottschalk, P Metz, H Gebhard, S Zysk, M E Eichhorn, T M Hernandez-Richter, V Jansson, A Veihelmann
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  ABSTRACT: Growing evidence supports the substantial pathophysiological impact of platelets on the development of rheumatoid arthritis. At present there are no methods for studying these cellular mechanisms in vivo. The aim of this study was to visualize and investigate platelet-endothelial cell interaction in the knee joint of mice with antigen-induced arthritis (AiA) by means of intravital microscopy. In 14 mice (Balbc) intravital microscopic assessment was performed on day 8 after AiA induction in two groups (controls, AiA). The severity of AiA was assessed by measuring knee joint swelling and by histological scoring. Ex vivo fluorescently labelled rolling and adherent platelets and leucocyte-endothelium interactions were investigated by intravital fluorescence microscopy. Swelling of the knee joint as well as histological score was significantly enhanced in arthritic animals compared with controls. In control mice intravital microscopy revealed low baseline rolling and sticking of leucocytes and fluorescently labelled platelets. AiA induced a significant increase in the fraction of rolling leucocytes (3 times) and rolling platelets (6 times) compared to the control group. Furthermore, AiA induction resulted in a significantly enhanced number of adherent leucocytes (3-fold) and adherent platelets (12-fold) in comparison with control animals. Platelet kinetics were directly analysed using intravital microscopy in the arthritic microcirculation in vivo for the first time. We provide the first evidence that platelets accumulate in arthritic vessels, indicating platelet activation due to AiA. Platelet recruitment and subsequent activation might play an important role in the pathogenesis of rheumatoid arthritis.
  Rheumatology 08/2005; 44(7):885-9. · 4.06 Impact Factor
• Article: In vivo interactions of platelets and leucocytes with the endothelium in murine antigen-induced arthritis: the role of P-selectin.

  M Schmitt-Sody, P Metz, A Klose, O Gottschalk, S Zysk, J Hausdorf, A Veihelmann, V Jansson
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  ABSTRACT: Platelets are thought to participate in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis (RA). We showed recently an in vivo increase in platelet-endothelial cell interactions in mice with antigen-induced arthritis (AiA). The underlying mechanisms are not yet clear. The aim of this study was to investigate the impact of P-selectin in AiA by means of intravital fluorescence microscopy (IVM). C57/Bl6 mice and P-selectin-deficient mice were divided into four groups (n = 7; control/AiA per strain). The extent of AiA was assessed by measuring knee joint swelling and by histological scoring. Rolling and adherent fluorescence-labelled platelets and leucocytes were investigated by IVM. In arthritic P-selectin-deficient mice (rolling: 0.05+/-0.01; adherent: 130+/-20 mm(-2)), compared to arthritic C57/Bl6 mice (rolling: 0.20+/-0.04; adherent: 1910+/-200 mm(-2)), platelet interaction was significantly reduced (p<0.05) and reached the level of both control groups without AiA. In addition, interaction of leucocytes in P-selectin-deficient arthritic animals (rolling: 0.12+/-0.06; adherent: 387+/-37 mm(-2)) was significantly decreased in comparison to arthritic C57/Bl6 animals (rolling: 0.21+/-0.06; adherent: 1492+/-284 mm(-2); p<0.05). Swelling of the knee joint and histological scoring were reduced in arthritic P-selectin-deficient mice compared to arthritic C57/Bl6 mice. We have demonstrated for the first time in vivo a significant decrease in the interaction of platelets and leucocytes with the endothelium in P-selectin-deficient mice with AiA and a reduction in clinical and histological symptoms of arthritis. These findings suggest that leucocyte-endothelial cell interactions depend at least partially on platelet P-selectin and therefore platelets may be responsible for the leucocyte tissue damage in AiA.
  Scandinavian Journal of Rheumatology 36(4):311-9. · 2.47 Impact Factor