title: Adsorptive depletion of alpha4 integrin(hi)- and CX3CR1hi-expressing proinflammatory monocytes in patients with ulcerative colitis.
abstract: BACKGROUND
  Two main functionally distinct monocytes phenotypes are known: the CD14(hi)CD16(-) "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.
  
  
  OBJECTIVE
  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 <or=4) after 5-10 GMA sessions. GMA induced a strong fall in the ratio (%) of CD14(+)CD16(+) to CD14(hi)CD16(-) monocytes, from 10.0 +/- 1.4 to 3.0 +/- 0.9. Further, expressions of alpha4 integrin (374.8 +/- 26.1 mean fluorescence intensity, MFI) and CX(3)CR1 (49.5 +/- 4.6 MFI) were significantly high on CD14(+)CD16(+)monocytes as compared with on CD14(hi)CD16(-) monocytes (169.2 +/- 17.2 and 33.2 +/- 3.6 MFI, respectively). Additionally, GMA significantly increased the ratio of the CD14(hi)CD16(-)CCR2(low) "immature" monocytes from 3.74 +/- 0.62 to 8.11 +/- 0.56 MFI.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba-shi, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Takeda
authors.forename: Toru
authors.initials: T
authors.lastname: Sato
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Katsuno
authors.forename: Tomoo
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000293:Adolescent; D000327:Adsorption; D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood* / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D039441:Integrin alpha4 / Q000276:immunology* / Q000378:metabolism; D007937:Leukapheresis / Q000379:methods*; D018950:Lipopolysaccharide Receptors / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011336:Probability; D054367:Receptors, CXCR3 / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: C515187:CXCR3 protein, human; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; D054367:Receptors, CXCR3; D017452:Receptors, IgG; D039441:Integrin alpha4