title: Investigating the role of proinflammatory CD16+ monocytes in the pathogenesis of inflammatory bowel disease.
abstract: Infiltrating monocytes and macrophages contribute to the initiation and perpetuation of mucosal inflammation characteristic for human inflammatory bowel disease (IBD). Peripheral blood monocytes expressing the low-affinity Fcgamma receptor CD16 have been identified previously as a major proinflammatory cell population, based on their unique cytokine secretion profile. However, the contribution of these cells to the pathogenesis of inflammatory bowel disease remains to be elucidated. Thus, in this study we investigated whether the peripheral CD16(+) monocyte count correlates with common IBD disease parameters, and whether these cells infiltrate the intestinal mucosa under inflammatory conditions. We observed that CD16(+) peripheral blood monocytes are increased significantly in active Crohn's disease, particularly in patients with high Crohn's disease activity index and colonic involvement. Furthermore, we found that CD16(+) cells are a major contributor to the inflammatory infiltrate in Crohn's disease mucosa, although their spontaneous migration through primary human intestinal endothelial cells is limited. Our data suggest that lamina propria, but not peripheral blood, CD16(+) monocytes are a crucial proinflammatory cell population in IBD, and a potential target for anti-inflammatory therapy.
authors.affiliation: Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. skoch2@emory.edu
authors.forename: S
authors.initials: S
authors.lastname: Koch
authors.forename: T
authors.initials: T
authors.lastname: Kucharzik
authors.forename: J
authors.initials: J
authors.lastname: Heidemann
authors.forename: A
authors.initials: A
authors.lastname: Nusrat
authors.forename: A
authors.initials: A
authors.lastname: Luegering
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002097:C-Reactive Protein / Q000378:metabolism; D040881:CD11a Antigen / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003093:Colitis, Ulcerative / Q000209:etiology / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000175:diagnosis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D058851:GPI-Linked Proteins; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D017452:Receptors, IgG / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D040881:CD11a Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D005938:Glucocorticoids; D053583:Interleukin-1beta; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein
references.citation: Scand J Immunol. 2009 Oct;70(4):368-76
references.pmid: 19751271
references.citation: Gastroenterology. 1976 Mar;70(3):439-44
references.pmid: 1248701
references.citation: Arthritis Rheum. 2004 May;50(5):1457-67
references.pmid: 15146415
references.citation: Inflamm Bowel Dis. 2000 Feb;6(1):21-33
references.pmid: 10701146
references.citation: Mucosal Immunol. 2008 Nov;1 Suppl 1:S5-9
references.pmid: 19079230
references.citation: Int Immunol. 2001 Dec;13(12):1571-81
references.pmid: 11717198
references.citation: J Exp Med. 2009 Aug 31;206(9):1883-97
references.pmid: 19652016
references.citation: Eur J Immunol. 2001 Jan;31(1):48-56
references.pmid: 11169437
references.citation: Inflamm Bowel Dis. 2007 Mar;13(3):284-90
references.pmid: 17206704
references.citation: J Immunol. 1996 Apr 1;156(7):2558-65
references.pmid: 8786319
references.citation: J Leukoc Biol. 2003 Jul;74(1):33-9
references.pmid: 12832440
references.citation: Eur J Immunol. 1993 Sep;23(9):2053-8
references.pmid: 7690321
references.citation: J Immunol. 1992 Jan 15;148(2):485-90
references.pmid: 1309559
references.citation: J Leukoc Biol. 2007 Mar;81(3):584-92
references.pmid: 17135573
references.citation: Virchows Arch. 2000 Oct;437(4):396-405
references.pmid: 11097365
references.citation: Am J Gastroenterol. 2008 May;103(5):1210-6
references.pmid: 18177452
references.citation: Gut. 1984 Jan;25(1):32-40
references.pmid: 6228498
references.citation: Blood. 1993 Nov 15;82(10):3170-6
references.pmid: 7693040
references.citation: Clin Exp Immunol. 1998 Jun;112(3):501-6
references.pmid: 9649222
references.citation: J Immunol. 2004 Apr 1;172(7):4410-7
references.pmid: 15034056
references.citation: Gut. 1995 Aug;37(2):225-34
references.pmid: 7557573
references.citation: Blood. 1989 Nov 15;74(7):2527-34
references.pmid: 2478233
references.citation: Immunobiology. 2004;209(1-2):11-20
references.pmid: 15481136
references.citation: J Clin Gastroenterol. 2007 Nov-Dec;41(10):874-88
references.pmid: 18090155
references.citation: J Exp Med. 2002 Aug 19;196(4):517-27
references.pmid: 12186843
references.citation: J Leukoc Biol. 2000 May;67(5):699-704
references.pmid: 10811011
references.citation: Gut. 2003 Apr;52(4):558-62
references.pmid: 12631669
references.citation: Am J Physiol Cell Physiol. 2005 Feb;288(2):C272-81
references.pmid: 15483224
references.citation: Arthritis Rheum. 2002 Oct;46(10):2578-86
references.pmid: 12384915
references.citation: Inflamm Bowel Dis. 2007 May;13(5):566-72
references.pmid: 17260384