Investigating the role of proinflammatory CD16+ monocytes in the pathogenesis of inflammatory bowel disease.
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.
Koch
S
S
Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. skoch2@emory.edu
Kucharzik
T
T
Heidemann
J
J
Nusrat
A
A
Luegering
A
A
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
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
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