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- Title
Adsorptive depletion of alpha4 integrin(hi)- and CX3CR1hi-expressing proinflammatory monocytes in patients with ulcerative colitis.
- Authors
Takeda, Shin-ichiro; Sato, Toru; Katsuno, Tatsuro; Nakagawa, Tomoo; Noguchi, Yoshiko; Yokosuka, Osamu; Saito, Yasushi
- 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.
- Subjects
MONOCYTES; PHENOTYPES; ULCERATIVE colitis; IMMUNOPATHOLOGY; ADRENOCORTICAL hormones; FLUORIMETRY; IMMUNOSUPPRESSIVE agents; ADSORPTION (Chemistry); ANTIGENS; CELL receptors; COMPARATIVE studies; FLOW cytometry; GRANULOCYTES; LEUKAPHERESIS; RESEARCH methodology; MEDICAL cooperation; NONPARAMETRIC statistics; PROBABILITY theory; RESEARCH; EVALUATION research; CASE-control method; THERAPEUTICS
- Publication
Digestive Diseases & Sciences, 2010, Vol 55, Issue 7, p1886
- ISSN
0163-2116
- Publication type
journal article
- DOI
10.1007/s10620-009-0974-2