Scientific corner

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

Shin-ichiro TakedaToru SatoTatsuro KatsunoTomoo NakagawaYoshiko NoguchiOsamu Yokosuka & Yasushi Saito

Dig Dis Sci 55, 1886–1895 (2010).

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 CD14hiCD16−CCR2low “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 D14hiCD16CCR2low “immature” monocytes; thus, GMA was associated with the emergence of less inflammatory monocyte phenotype in circulation.

Scientific corner

In vivo modulation of leukocyte trafficking receptor following therapeutic purging of myeloid cells: implications for treatment of HIV infection and other immune disorders

Priscilla Biswas Barbara Mantelli Alberto Beretta Clinical Immunology 109 (2003) 355–358 DOI: 10.1016/j.clim.2003.07.001 

Therapeutic purging of myeloid cells (monocytes and granulocytes) (MYP) has been proposed as a treatment of severe inflammatoryconditions like ulcerative colitis and rheumatoid arthritis. Although direct purging of inflammatory cells contributes to its efficacy, the precise mechanism of action is still unclear. We have tested MYP in a pilot study on 12 patients with chronic HIV infection, of whom 6 underwent MYP. Three/6 MYP patients and none of the controls displayed a strong and long-lasting decrease of cells expressing CXCR3,a major chemokine receptor responsible for trafficking of inflammatory cells. In these three patients, the number of circulating CD4 T cells increased during treatment. The data provide a rational for the use of MYP as a therapeutic tool acting via the modulation of immune cell trafficking

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