, Volume 55, Issue 7, pp 1886-1895

Adsorptive Depletion of α4 Integrinhi- and CX3CR1hi-Expressing Proinflammatory Monocytes in Patients with Ulcerative Colitis

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Abstract

Background

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.

Aim

To selectively deplete circulating proinflammatory CD14+CD16+ monocyte phenotype.

Methods

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.

Results

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 CD14hiCD16CCR2low “immature” monocytes from 3.74 ± 0.62 to 8.11 ± 0.56 MFI.

Conclusions

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 CD14hiCD16CCR2low “immature” monocytes; thus GMA was associated with the emergence of less inflammatory monocyte phenotype in circulation.