Interaction of monocytes from patients with psoriatic arthritis with cultured microvascular endothelial cells

The aim of this study was to investigate the interaction of monocytes of th e 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 oth er cell surface molecules in psoriatic arthritis and control monocytes was investigated by quantitative flow cytometry. The receptor densities of thes e molecules were determined in terms of monoclonal antibody (mAb) binding s ites. Cocultivation experiments including peripheral blood mononuclear cell s and HDMEC were performed to determine the adhesion to and transmigration through activated or resting endothelial cell monolayers. In order to achie ve optimal responses of cellular functions, activation for adhesion experim ents was induced by lipopolysaccharide (LPS), while in transmigration exper iments the endothelial cells were activated by TNF-alpha. For transendothel ial migration studies HDMEC cultivated ion collagen gels were used. In the supernatants of cocultivated cells the cytokines IL-6 and IL-8 were determi ned by ELISA. A significantly reduced expression of CD11b in nonactivated p soriatic arthritis peripheral blood monocytes compared to control monocytes was verified (mean number of adhesion molecules/cell: 33756 +/- 10138 vs 6 1023 +/- 6925). In agreement with these findings, adhesion to, as well as t ransendothelial migration through, activated HDMEC was found to be signific antly reduced in psoriatic arthritis monocytes, Transendothelial migration engendered an enrichment of monocytes in the migrated cell fraction for bot h control and psoriatic arthritis peripheral blood mononuclear cells. The a ctivation of HDMEC by LPS induced a highly significantly enhanced cytokine release for IL-6 and IL-8, irrespective of the origin of monocytes (psoriat ic arthritis vs. controls). However, IL-8 production in the supernatants of nonactivated monocytes/HDMEC cocultures was significantly reduced in the c ase of monocytes from psoriatic arthritis patients (6650 +/- 2489.32 pg/ml) vs 9280.00 +/- 3209.51 pg/ml in control patients, Impaired adhesion as wel l 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 r educed IL-8 production also corresponds to a diminished cellular interactio n under nonflow conditions. These results support the view that there are s ystemic immunological alterations in psoriatic arthritis patients. (C) 2000 Academic Press.