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Interaction of monocytes from patients with psoriatic arthritis with cultured microvascular endothelial cells
J Neumüller1, A Dunky, H Burtscher
1Institute of Histology and Embryology, University of Vienna, A-1090 Vienna, Austria.
Abstract:
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.
Insights
Psoriatic arthritis monocytes show reduced adhesion and migration due to lower CD11b expression. This impaired cell interaction suggests systemic immune changes in psoriatic arthritis patients.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Psoriatic arthritis (PsA) is a chronic inflammatory disease with systemic manifestations.
- Monocyte interaction with endothelial cells is crucial in inflammatory processes.
- Understanding these interactions in PsA may reveal disease mechanisms.
Purpose of the Study:
- To investigate monocyte interactions with human dermal microvascular endothelial cells (HDMEC) in PsA patients versus controls.
- To analyze the expression of adhesion molecules on PsA monocytes.
- To assess monocyte adhesion and transmigration through HDMEC monolayers.
Main Methods:
- Quantitative flow cytometry to measure cell surface molecule expression on monocytes.
- Co-cultivation of peripheral blood mononuclear cells (PBMCs) with HDMEC.
- Stimulation of cellular functions using lipopolysaccharide (LPS) and TNF-alpha.
- Enzyme-linked immunosorbent assay (ELISA) for cytokine (IL-6, IL-8) quantification.
Main Results:
- Significantly reduced expression of CD11b (MAC-1) on nonactivated PsA monocytes compared to controls.
- Significantly reduced adhesion to and transendothelial migration through activated HDMEC by PsA monocytes.
- Reduced IL-8 production by PsA monocytes in nonactivated co-cultures.
Conclusions:
- Impaired monocyte adhesion and transendothelial migration in PsA are linked to reduced MAC-1 expression.
- Diminished IL-8 production correlates with reduced cellular interaction.
- Findings suggest systemic immunological alterations in psoriatic arthritis patients.