The aim of this study was to investigate the interaction of monocytes of the peripheral blood of patients with psoriatic arthritis with cultured human dermal microvascular endothelial cells (HDMEC) compared to monocytes from control persons. The surface expression of adhesion molecules (ADM) and other cell surface molecules in psoriatic arthritis and control monocytes was investigated by quantitative flow cytometry. The receptor densities of these molecules were determined in terms of monoclonal antibody (mAb) binding sites. Cocultivation experiments including peripheral blood mononuclear cells and HDMEC were performed to determine the adhesion to and transmigration through activated or resting endothelial cell monolayers. In order to achieve optimal responses of cellular functions, activation for adhesion experiments was induced by lipopolysaccharide (LPS), while in transmigration experiments the endothelial cells were activated by TNF-alpha. For transendothelial migration studies HDMEC cultivated on collagen gels were used. In the supernatants of cocultivated cells the cytokines IL-6 and IL-8 were determined by ELISA. A significantly reduced expression of CD11b in nonactivated psoriatic arthritis peripheral blood monocytes compared to control monocytes was verified (mean number of adhesion molecules/cell: 33,756 +/- 10,138 vs 61,023 +/- 6925). In agreement with these findings, adhesion to, as well as transendothelial migration through, activated HDMEC was found to be significantly reduced in psoriatic arthritis monocytes. Transendothelial migration engendered an enrichment of monocytes in the migrated cell fraction for both control and psoriatic arthritis peripheral blood mononuclear cells. The activation of HDMEC by LPS induced a highly significantly enhanced cytokine release for IL-6 and IL-8, irrespective of the origin of monocytes (psoriatic arthritis vs. controls). However, IL-8 production in the supernatants of nonactivated monocytes/HDMEC cocultures was significantly reduced in the case of monocytes from psoriatic arthritis patients (6650 +/- 2489.32 pg/ml) vs 9280.00 +/- 3209.51 pg/ml in control patients. Impaired adhesion as well as transendothelial migration of monocytes derived from peripheral blood of psoriatic arthritis patients can be explained by the reduced expression of adhesion molecules MAC-1 (CD11b/CD18) at the surface of monocytes. The reduced IL-8 production also corresponds to a diminished cellular interaction under nonflow conditions. These results support the view that there are systemic immunological alterations in psoriatic arthritis patients.
Copyright 2001 Academic Press.