Adsorptive depletion of α4 integrin(hi)- and CX3CR1(hi)-expressing proinflammatory monocytes in patients with ulcerative colitis
We found high expressions of alpha4 integrin and CX(3)CR1 on monocytes in patients with active UC, known to promote the extravasation of CD14(+)CD16(+) monocytes into the mucosa. GMA effectively depletes CD14(+)CD16(+) monocytes and concomitantly increases CD14(hi)CD16(-)CCR2(low) “immature” monocytes; thus GMA was associated with the emergence of less inflammatory monocyte phenotype in circulation.
Granulocyte and Monocyte Adsorption Apheresis Therapy Modulates Monocyte-Derived Dendritic Cell Function in Patients With Ulcerative Colitis
The aim of this study was to elucidate the molecular mechanisms responsible for the therapeutic effects of granulocyte and monocyte adsorption apheresis (GMA). We investigated the alterations in circulating monocyte subsets and monocyte-derived dendritic cell (moDC) function after GMA therapy in ulcerative colitis (UC) patients. Eighteen patients with UC were enrolled: 14 patients were responders, and 4 patients were non-responders. Peripheral venous blood was obtained within 5 min before and 5 min after GMA therapy. Flow cytometric analysis for monocyte markers (CD14/CD16) was then performed. Monocyte-derived dendritic cells were obtained and alterations in their phenotype were analyzed by flow cytometry. Their function was also analyzed in a mixed lymphocyte reaction assay between allo-naïve T lymphocytes. Flow cytometric analysis for intracellular interferon (IFN)-γ (T-helper 1 cells) and interleukin (IL)-4 (T-helper 2 cells) was then performed for the stimulated T lymphocytes. In patients who responded to GMA, the average numbers of monocytes, especially CD16+ monocytes, were significantly decreased after therapy (P < 0.05). In responders, post-GMA moDCs expressed significantly lower CD80 and B7-DC, which are one of the stimulation and maturation markers of dendritic cells, compared to pre-GMA moDCs. CD83, CD86 and human leukocytcde antigen-DR also showed a tendency to decrease. In responders, naïve T lymphocytes stimulated with post-GMA moDCs produced significantly less IFN-γ and IL-4 compared to those stimulated with pre-GMA moDCs. The results of our study show that some of the immunosuppressive effects of GMA therapy may be associated with the modulation of monocyte subsets and moDC function.
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