Role of selectins on IgE‐mediated skin reaction

Abstract

1 Selectins play an important role on leukocytes in®ltration into in¯ammatory tissues. To understand the role of selectins, we investigated the eects of selectin-IgG chimeras and anti selectin antibodies on the murine IgE-mediated skin in¯ammation model. 2 Biphasic skin reactions were induced by intradermal challenge with ovalbumin (OA) to ears of actively sensitized mice. This reaction was characterized by immediate and late phase responses observed as which were induced via a rapid increase in capillary permeability and leukocyte in®ltration, respectively. The expression of E-selectin mRNA was signi®cantly increased to reach its highest level at 2 h after OA challenge. 3 E-, P-, and L-selectin-IgG chimeras inhibited the late phase responses, i.e. ear swelling, neutrophil in®ltration and eosinophil in®ltration at 24 h after OA challenge in a dose-dependent manner at dose range of 0.1 ± 10 mg kg 71 , i.v. Antiselectin antibodies did not inhibit the increase of ear swelling. But anti E-and P-selectin antibodies signi®cantly inhibited neutrophil in®ltration and eosinophil in®ltration. 4 These results indicate that selectins play an important role on the late phase response of the murine IgE-mediated skin in¯ammation model by mediating in¯ammatory cell adhesion to endothelium.

Therapeutic potential of a novel synthetic selectin blocker, OJ‐R9188, in allergic dermatitis

“…In the IgE‐mediated skin reaction in ears of actively sensitized mice, ear swelling appears in the early phase (1 h after antigen challenge) and the late phase (24 h after antigen challenge), and infiltration of neutrophils and eosinophils into the tissue occurs in the late phase. We have reported that selectins play an important role in the late phase response in this model (Wada et al ., 2000). When OJ‐R9188 (1 – 10 mg kg −1 ), TBC‐1269 (30 mg kg −1 ), fucoidin (10 mg kg −1 ) and sLe x (10 mg kg −1 ) were given intravenously just before OA challenge, they slightly inhibited ear swelling in the late phase reaction.…”

“…Thus, the expression of E‐selectin may be involved in the pathogenesis of such skin inflammation. We reported that the expression of E‐selectin mRNA was significantly increased 2 h after OA challenge and that E‐selectin may be involved in the leukocyte infiltration into the skin during the late phase response of the IgE‐mediated skin reaction in mice (Wada et al ., 2000).…”

“…In previous studies, we have demonstrated that the selectins play important roles in the late phase response of the IgE‐mediated skin reaction in mice (Wada et al ., 2000). We have been studying low molecular weight selectin blockers that prevent the inflammatory skin reaction.…”

Updates from the British Association of Dermatologists 82nd Annual Meeting, 9-12 July 2002, Edinburgh, U.K.

“…Emerging immunotherapies have been at the forefront of new psoriatic treatments in recent years. Selectins play an important role in leucocyte inflammation in inflammatory skin 31 . Anti‐E‐selectin antibodies have been shown significantly to inhibit neutrophil and eosinophil infiltration 31 .…”

“…Selectins play an important role in leucocyte inflammation in inflammatory skin 31 . Anti‐E‐selectin antibodies have been shown significantly to inhibit neutrophil and eosinophil infiltration 31 . Scientifically targeting skin‐homing T lymphocytes seems an attractive option and the use of an antibody directed to E‐selectin seems a rational approach.…”