Adsorptive depletion of alpha4 integrin(hi)- and CX3CR1hi-expressing proinflammatory monocytes in patients with ulcerative colitis.
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.
Takeda
Shin-ichiro
S
Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba-shi, Japan.
Sato
Toru
T
Katsuno
Tatsuro
T
Nakagawa
Tomoo
T
Noguchi
Yoshiko
Y
Yokosuka
Osamu
O
Saito
Yasushi
Y
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
C515187:CXCR3 protein, human; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; D054367:Receptors, CXCR3; D017452:Receptors, IgG; D039441:Integrin alpha4