Adsorptive Depletion of α4 Integrinhi- and CX3CR1hi-Expressing Proinflammatory Monocytes in Patients with Ulcerative Colitis
- 12 November 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Digestive Diseases and Sciences
- Vol. 55 (7), 1886-1895
- https://doi.org/10.1007/s10620-009-0974-2
Abstract
Two main functionally distinct monocytes phenotypes are known: the CD14hiCD16− “classical” and the CD14+CD16+ “proinflammatory” phenotypes. The latter phenotype is elevated in patients with ulcerative colitis (UC) and is suspected to have a major role in the immunopathogenesis of UC. To selectively deplete circulating proinflammatory CD14+CD16+ monocyte phenotype. Seven corticosteroid-naïve patients with UC (clinical activity index = 8.7 ± 1.3) and seven healthy subjects were included. In patients with UC, granulocyte/monocyte adsorption (GMA) was done with an Adacolumn that selectively adsorbs leucocytes of the myeloid lineage. Blood from all subjects at baseline and from the patients immediately after the first GMA session was processed. Isolated monocytes were subjected to fluorescence-activated cell sorter analyses. The seven UC patients achieved remission (CAI ≤4) after 5–10 GMA sessions. GMA induced a strong fall in the ratio (%) of CD14+CD16+ to CD14hiCD16− monocytes, from 10.0 ± 1.4 to 3.0 ± 0.9. Further, expressions of α4 integrin (374.8 ± 26.1 mean fluorescence intensity, MFI) and CX3CR1 (49.5 ± 4.6 MFI) were significantly high on CD14+CD16+monocytes as compared with on CD14hiCD16− monocytes (169.2 ± 17.2 and 33.2 ± 3.6 MFI, respectively). Additionally, GMA significantly increased the ratio of the CD14hiCD16−CCR2low “immature” monocytes from 3.74 ± 0.62 to 8.11 ± 0.56 MFI. We found high expressions of α4 integrin and CX3CR1 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 CD14hiCD16−CCR2low “immature” monocytes; thus GMA was associated with the emergence of less inflammatory monocyte phenotype in circulation.Keywords
This publication has 58 references indexed in Scilit:
- Selective white cell apheresis reduces relapse rates in patients with IBD at significant risk of clinical relapseInflammatory Bowel Diseases, 2008
- In patients with ulcerative colitis, adsorptive depletion of granulocytes and monocytes impacts mucosal level of neutrophils and clinically is most effective in steroid naïve patientsDigestive and Liver Disease, 2008
- A Randomized, Double-Blind, Sham-Controlled Study of Granulocyte/Monocyte Apheresis for Active Ulcerative ColitisGastroenterology, 2008
- Monocyte-Mediated Defense Against Microbial PathogensAnnual Review of Immunology, 2008
- Unravelling the pathogenesis of inflammatory bowel diseaseNature, 2007
- Demonstration of Low-Regulatory CD25High+CD4+ and High-Pro-inflammatory CD28−CD4+ T-Cell Subsets in Patients with Ulcerative Colitis: Modified by Selective Granulocyte and Monocyte Adsorption ApheresisDigestive Diseases and Sciences, 2007
- Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sitesJCI Insight, 2007
- Enhanced Recruitment of CX3CR1+ T Cells by Mucosal Endothelial Cell–Derived Fractalkine in Inflammatory Bowel DiseaseGastroenterology, 2007
- A Retrospective Search for Predictors of Clinical Response to Selective Granulocyte and Monocyte Apheresis in Patients With Ulcerative ColitisDigestive Diseases and Sciences, 2006
- Monocyte and macrophage heterogeneityNature Reviews Immunology, 2005