Increased Neutrophil Adherence in Psoriasis: Role of the Human Endothelial Cell Receptor Thy-1 (CD90)

Abstract

The chronic inflammatory skin disease psoriasis is characterized by prominent skin infiltration by neutrophils and microabscess formation. The adhesion of leukocytes and subsequent transmigration through the activated endothelium is one prerequisite for the accumulation of these cells in skin. In recent studies, the human Thy-1 (CD90) was characterized as an adhesion molecule on activated endothelial cells (ECs) mediating the adhesion of neutrophils via the interaction with the beta2-integrin Mac-1. Based on these novel findings, we compared the roles of Thy-1 and ICAM-1 in the adhesion of neutrophils from patients with psoriasis to activated ECs. The adhesion of peripheral blood neutrophils of patients suffering from psoriasis to Thy-1-transfected cells as well as to activated, Thy-1-expressing human dermal microvascular ECs (HDMECs) is distinctly increased in comparison to the adhesion of neutrophils from healthy controls. In contrast, adherence of psoriatic neutrophils to ICAM-1 transfectants is, if at all, only slightly enhanced compared to healthy controls. The interaction of healthy as well as psoriatic polymorphonuclear cells to Thy-1 transfectants and HDMECs was significantly inhibited by blocking Thy-1 on ECs or its receptor Mac-1 on neutrophils, indicating the importance of this interaction for the adhesion of neutrophils to activated endothelium. In conclusion, our data indicate that the adhesion of neutrophils to activated ECs mediated by Thy-1/Mac-1 interaction is an important attachment mechanism facilitating their subsequent migration into lesional psoriatic skin.

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

“…Fibroblasts or activated HDMEC themselves did not produce MMP-9. Preincubation with a function-blocking anti-Thy-1 antibody (clone BC9; [24,25]) clearly decreased the MMP-9 secretion of neutrophils induced by interaction with activated HDMEC (Fig. 4A) as well as with fibroblasts (Fig.…”

“…HDMEC were stimulated with 20 ng/mL rhTNF-a (Tebu). In blocking experiments, fibroblasts or HDMEC were preincubated with the anti-Thy-1 antibody AS02, the adhesion-inhibiting anti-Thy-1 antibody BC9 [25], or with an isotype control antibody for 20 min. Accordingly, neutrophils were incubated with an anti-CD18 antibody (1 lg/4 Â 10 5 cells), an anti-MHC I antibody (1 lg/4 Â 10 5 cells) or without antibody for 20 min at 4 C. Antibodies were removed by careful washing.…”

CD90 Expression on human primary cells and elimination of contaminating fibroblasts from cell cultures

“…NHEKs do not express CD90 (Wittmann et al 2005). Activated HUVECs express CD90, while non-activated HUVECs do not (Wetzel et al 2006;Saalbach et al 2000). In this study, non-activated HUVECs were analyzed for CD90 expression.…”

Dynamic catch of a Thy-1–α5β1+syndecan-4 trimolecular complex

“…Thy-1 (CD90) is a heavily N-glycosylated single v-type immunoglobulin (Ig) domaincontaining glycoprotein, probably of primordial origin within the immunoglobulin superfamily 2 . It is linked to the outer leaflet of the plasma membrane via a carboxy-terminal glycophosphatidylinositol anchor, where it binds integrins in a variety of tissue-specific contexts, including a M b 2 (Mac-1) on leukocytes 3,4 , a v b 3 on melanoma cells 5 and neurons 6,7 , and a v b 5 on lung fibroblasts 8 . For a full review, see ref.…”