Decreased expression levels of L-selectin on subsets of leucocytes and increased serum L-selectin in severe psoriasis

Abstract

L-selectin is a leucocyte adhesion molecule involved in leucocyte interactions with vascular endothelial cells. Following leucocyte activation L-selectin is endoproteolytically released from the cell surface. To assess whether psoriasis vulgaris results in systemic leucocyte activation, we examined expression levels of L-selectin on subsets of peripheral blood leucocytes from patients with psoriasis (n = 25) and normal control subjects. Serum levels of soluble L-selectin were quantified by ELISA in patients with psoriasis (n = 75), pustulosis palmaris et plantaris, and contact dermatitis, as well as normal control subjects. Psoriasis severity was evaluated by psoriasis area and severity index (PASI). L-selectin expression levels on CD4+ T cells, B cells, monocytes, and neutrophils from patients with severe-type psoriasis (PASI > or = 15) was significantly decreased compared with leucocytes from normal control subjects. Furthermore, L-selectin expression on CD4+ T cells showed good inverse correlation with PASI scores. Monocyte L-selectin expression was restored when the skin lesions of psoriasis were remitted. The frequencies of L-selectin+ CD4+ T cells or L-selectin+ CD8+ T cells from patients with psoriasis were almost normal. Serum L-selectin levels in patients with severe-type psoriasis were significantly higher than those in normal control subjects. These results suggest that subsets of leucocytes may be activated in psoriasis, and that L-selectin expression levels on some leucocyte subsets, especially CD4+ T cells, tend to correlate with disease severity of psoriasis.

Fig. 1

Expression of L-selectin (CD62L) by CD4⁺ T cells (a), CD20⁺ B cells (b), CD14⁺ monocytes (c), CD16⁺ neutrophils (d) from patients with severe-type psoriasis and normal control subjects. All samples were stained and analysed sequentially by two-colour or three-colour flow cytometry with identical instrument settings. Additionally, CD4⁺ T cells were identified by staining with PerCP-conjugated MoAb, and the gated population of cells was then examined for the expression of CD45RO and L-selectin by flow cytometry (e). Horizontal dashed lines are provided for reference. These results are representative of those obtained from nine sets of patients.

Fig. 2

Expression of cell surface L-selectin by CD4⁺ (a) or CD8⁺ T cells (b), CD20⁺ B cells (c), CD14⁺ monocytes (d), and CD16⁺ neutrophils (e) from patients with severe-type psoriasis (Severe Pso.; psoriasis area and severity index (PASI) ≥15), mild to moderate-type psoriasis (Mild Pso.; PASI <15), and normal control subjects. L-selectin expression levels were assessed by two-colour immunofluorescence staining with flow cytometric analysis as shown in Fig. 1. The horizontal bar indicates the mean value for each group.

Fig. 3

Expression levels of L-selectin on CD4⁺ (a) or CD8⁺ T cells (b), CD20⁺ B cells (c), CD14⁺ monocytes (d), and CD16⁺ neutrophils (e) versus psoriasis area and severity index (PASI) scores in patients with psoriasis vulgaris.

Fig. 4

Expression levels of L-selectin on CD4⁺ T cells (a), CD20⁺ B cells (b), CD14⁺ monocytes (c), and CD16⁺ neutrophils (d) from patients whose psoriasis area and severity index (PASI) scores decreased >50% after treatment. The patients were treated with photochemotherapy (○), oral cyclosporin A (Δ), or topical corticosteroid ointment (□).

Fig. 5

The frequencies of L-selectin⁺ CD4⁺ (a) or CD8⁺ T cells (b) from patients with severe-type psoriasis vulgaris (Severe Pso.), mild to moderate-type psoriasis vulgaris (Mild Pso.), and normal control subjects. The frequencies of l-selectin⁺ lymphocytes were determined by two-colour immunofluorescence staining with flow cytometric analysis. All samples were stained and analysed sequentially by flow cytometry in parallel with the use of identical instrument settings.

Fig. 6

Serum levels of sL-selectin in patients with severe-type psoriasis vulgaris (Severe Pso.), mild to moderate-type psoriasis vulgaris (Mild Pso.), pustulosis palmaris et plantaris (PPP), contact dermatitis (Contact Derm.), and normal control subjects (CTL). Horizontal bars indicate the mean value for each group.