Pan-selectin antagonism improves psoriasis manifestation in mice and man (original) (raw)

Abstract

The selectin family of vascular cell adhesion molecules is comprised of structurally related carbohydrate binding proteins, which mediate the initial rolling of leukocytes on the activated vascular endothelium. Because this process is one of the crucial events in initiating and maintaining inflammation, selectins are proposed to be an attractive target for the development of new antiinflammatory therapeutics. Here, we demonstrate that the synthetic pan-selectin antagonist bimosiamose is effective in pre-clinical models of psoriasis as well as in psoriatic patients. In vitro bimosiamose proved to be inhibitory to E- or P-selectin dependent lymphocyte adhesion under flow conditions. Using xenogeneic transplantation models, bimosiamose reduced disease severity as well as development of psoriatic plaques in symptomless psoriatic skin. The administration of bimosiamose in patients suffering from psoriasis resulted in a reduction of epidermal thickness and lymphocyte infiltration. The clinical improvement was statistically significant (_P_=0.02) as analyzed by comparison of psoriasis area and severity index before and after treatment. Assessment of safety parameters showed no abnormal findings. These data suggest that pan-selectin antagonism may be a promising strategy for the treatment of psoriasis and other inflammatory diseases.

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Abbreviations

SCID:

Severe combined immunodeficiency

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Acknowledgements

The authors thank Petra Lindenberg for excellent technical assistance and Dr. Michael Schön for critical reading of the manuscript. This work was supported by grants of the Ministry of Economics of the State of Brandenburg and the European Union.

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Authors and Affiliations

1. Department of Dermatology and Allergy, University Hospital Charité, Schumannstr. 20/21, 10117, Berlin, Germany
   Markus Friedrich, Sandra Philipp, Nina Ludwig & Wolfram Sterry
2. Revotar Biopharmaceuticals AG, Neuendorfstr. 24a, 16761, Hennigsdorf, Germany
   Daniel Bock, Sabine Schroeter-Maas, Ewald Aydt, Rainer Zahlten & Gerhard Wolff
3. Department of Dermatology, The University of Michigan, 1301 Catherine Road, Box 0602, Ann Arbor, MI, 48109, USA
   Sewon Kang & Tomas Norman Dam
4. Interdisciplinary group of Molecular Immunopathology, Dermatology/Med.Immunology, University Hospital Charité, Schumannstr. 20/21, 10117, Berlin, Germany
   Markus Friedrich, Sandra Philipp, Nina Ludwig, Robert Sabat & Kerstin Wolk

Authors

1. Markus Friedrich
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2. Daniel Bock
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3. Sandra Philipp
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4. Nina Ludwig
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5. Robert Sabat
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6. Kerstin Wolk
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7. Sabine Schroeter-Maas
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8. Ewald Aydt
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9. Sewon Kang
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10. Tomas Norman Dam
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11. Rainer Zahlten
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12. Wolfram Sterry
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13. Gerhard Wolff
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Corresponding author

Correspondence toDaniel Bock.

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Markus Friedrich and Daniel Bock equally contributed to the study

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Friedrich, M., Bock, D., Philipp, S. et al. Pan-selectin antagonism improves psoriasis manifestation in mice and man.Arch Dermatol Res 297, 345–351 (2006). https://doi.org/10.1007/s00403-005-0626-0

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• Received: 08 August 2005
• Revised: 01 November 2005
• Accepted: 02 November 2005
• Published: 16 December 2005
• Issue Date: February 2006
• DOI: https://doi.org/10.1007/s00403-005-0626-0

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