title: Pan-selectin antagonism improves psoriasis manifestation in mice and man.
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.
authors.affiliation: Department of Dermatology and Allergy, University Hospital Charité, Schumannstr. 20/21, 10117 Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Friedrich
authors.forename: Daniel
authors.initials: D
authors.lastname: Bock
authors.forename: Sandra
authors.initials: S
authors.lastname: Philipp
authors.forename: Nina
authors.initials: N
authors.lastname: Ludwig
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.forename: Sabine
authors.initials: S
authors.lastname: Schroeter-Maas
authors.forename: Ewald
authors.initials: E
authors.lastname: Aydt
authors.forename: Sewon
authors.initials: S
authors.lastname: Kang
authors.forename: Tomas Norman
authors.initials: TN
authors.lastname: Dam
authors.forename: Rainer
authors.initials: R
authors.lastname: Zahlten
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolff
mesh_terms: D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D004817:Epidermis / Q000737:chemistry / Q000473:pathology; D005260:Female; D018922:HL-60 Cells; D006586:Hexanes / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019169:Jurkat Cells; D007962:Leukocytes / Q000473:pathology / Q000502:physiology; D008297:Male; D008358:Mannose / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D019007:P-Selectin / Q000032:analysis / Q000502:physiology*; D010865:Pilot Projects; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D006586:Hexanes; D019007:P-Selectin; C496819:bimosiamose; D008358:Mannose