Glycosylphosphatidylinositol (GPI)‐anchored membrane proteins are constitutively down‐regulated in psoriatic skin

Abstract

Hyperproliferation of keratinocytes (KCs) in psoriasis has been found to be associated with excessive activation of a phospholipase C (PLC)/protein kinase C (PKC) signal transduction system. The molecular species of PLCs which are activated in psoriasis have not been thoroughly investigated. It was envisaged that if glycosylphosphatidylinositol (GPI)-specific PLC was activated in the membrane of psoriatic epidermal cells, it would render these cells devoid of those proteins which are anchored to the cell membrane through their GPI moiety. In order to test this possibility, four GPI proteins (CD16, CD55, CD58, and CD59) were determined immunohistochemically in normal and psoriatic skin. In normal skin, CD55 and CD59 were strongly expressed on epithelium and vascular structures, whereas CD16 and CD58 were strongly expressed only on epithelium. The expression of all four GPI proteins was decreased in non-lesional psoriatic skin and virtually abolished in lesional psoriatic skin. A control transmembrane protein, CD46, was strongly expressed in normal and non-lesional psoriatic skin, and its expression was not significantly decreased in psoriatic lesions. The absence or reduction of GPI proteins was not seen in the lesions of several other inflammatory and proliferative diseases studied.

Glycosylphosphatidylinositol-anchored Proteins Regulate Transforming Growth Factor-β Signaling in Human Keratinocytes

“…Hence, it is likely that r150 binds to TGF-␤1 independently of the TGF-␤ signaling receptors when attached to the cell surface. This is in contrast to the type I receptor and endoglin, which recognize TGF-␤ only when bound to the type II receptor (12,18,25). Thus, the membrane-anchored form of r150 may regulate TGF-␤1 binding to its receptors and hence signaling.…”

“…CD59, a 21-kDa GPI-anchored protein expressed on keratinocytes, was used as a marker for the cloning of GPI anchor-deficient cells. CD59 is an inhibitor of the membrane attack complex (25,26). After EMS treatment, cells were stained with fluorescein isothiocyanate-conjugated anti-CD59 antibody and negatively sorted by FACS analysis.…”

A knock-out model of paroxysmal nocturnal hemoglobinuria: Pig-a(-) hematopoiesis is reconstituted following intercellular transfer of GPI-anchored proteins.

“…After treatment with the antibody to CD52 was discontinued, cells with the GPI-AP-phenotype gradually disappeared, a result that argues against any intrinsic proliferative advantage conferred by the PIG-A mutation, at least for lymphocytes. Immune selection for GPI-AP deficiency may also occur in the autoimmune disease psoriasis; GPI-AP expression was lower than normal in nonlesional psoriatic skin and virtually absent in lesional psoriatic skin (48). In PNH, deficiency of GPI-AP on the surface of the affected clone(s) may not become absolute until the progeny leave the close proximity of GPI-AP+ cells present in the bone marrow (49) (45) with only partial inactivation of the PIG-A gene product or are the result of GPI-AP exchange.…”

Thy-1 (CD90) Is an Interacting Partner for CD97 on Activated Endothelial Cells

“…Moreover, pretreatment of activated EC with Thy-1-or CD55-blocking mAb resulted in stronger inhibition of adherence by the Thy-1-blocking mAb. Additionally, in normal human skin, CD55 is present in vascular structures, but its expression is decreased in nonlesional psoriatic skin and virtually abolished in lesional psoriatic skin (25). Furthermore, CD97-CD55 interaction is not involved in human leukocyte adhesion to porcine EC in transplantation models (26).…”