Document Detail


Adsorptive depletion of alpha4 integrin(hi)- and CX3CR1hi-expressing proinflammatory monocytes in patients with ulcerative colitis.
MedLine Citation:
PMID:  19908144     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. 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 <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:
Shin-ichiro Takeda; Toru Sato; Tatsuro Katsuno; Tomoo Nakagawa; Yoshiko Noguchi; Osamu Yokosuka; Yasushi Saito
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2009-11-12
Journal Detail:
Title:  Digestive diseases and sciences     Volume:  55     ISSN:  1573-2568     ISO Abbreviation:  Dig. Dis. Sci.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-17     Completed Date:  2010-07-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902782     Medline TA:  Dig Dis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1886-95     Citation Subset:  AIM; IM    
Affiliation:
Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba-shi, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adsorption
Adult
Antigens, CD14 / immunology*,  metabolism
Case-Control Studies
Colitis, Ulcerative / blood*,  physiopathology,  therapy*
Female
Flow Cytometry
Granulocytes / immunology,  metabolism
Humans
Immunosuppressive Agents / therapeutic use
Integrin alpha4 / immunology*,  metabolism
Leukapheresis / methods*
Male
Middle Aged
Monocytes / immunology,  metabolism
Probability
Receptors, CXCR3 / immunology*,  metabolism
Receptors, IgG / immunology,  metabolism
Statistics, Nonparametric
Young Adult
Chemical
Reg. No./Substance:
0/Antigens, CD14; 0/CXCR3 protein, human; 0/Immunosuppressive Agents; 0/Receptors, CXCR3; 0/Receptors, IgG; 143198-26-9/Integrin alpha4

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