title: Activated eosinophils in association with enteric nerves in inflammatory bowel disease.
abstract: Enteric neural dysfunction leads to increased mucous production and dysmotility in inflammatory bowel disease (IBD). Prior studies have shown that tissue eosinophilia is related to disease activity. We hypothesized that interactions between eosinophils and nerves contribute to neural dysfunction in IBD. Tissue from patients with intractable IBD, endoscopic biopsies from patients with steroid responsive IBD, both when active and quiescent, and control tissue were studied. Immunohistochemical studies showed that eosinophils localize to nerves in the mucosal layer of patients with Crohn's disease (CD) (p<0.001) and ulcerative colitis (UC), (p<0.01). Eosinophils localized to substance P and choline acetyltransferase (ChAT) immunostained nerves. Real time PCR of laser capture micro-dissected enteric ganglia demonstrated Intercellular Adhesion Molecule 1 (ICAM-1) mRNA was increased 7-fold in UC (n = 4), (p = 0.03), and 10-fold in CD (n = 3), (p = 0.05). Compared with controls, eotaxin-3 (CCL-26) mRNA was increased 9-fold in UC (p = 0.04) and 15-fold in CD (p = 0.06). Eosinophil numbers correlated with disease activity, while deposition of major basic protein (MBP) and eosinophil Transforming Growth Factor β-1 (TGFβ-1) expression were seen in therapeutically responsive disease. These data indicate a significant localization of eosinophils to nerves in IBD, mediated through neurally expressed ICAM-1 and eotaxin-3. This cell/neural interaction may influence the function of nerves and contribute to symptoms in IBD.
authors.affiliation: Departments of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Smyth
authors.forename: Nadim
authors.initials: N
authors.lastname: Akasheh
authors.forename: Sara
authors.initials: S
authors.lastname: Woods
authors.forename: Elaine
authors.initials: E
authors.lastname: Kay
authors.forename: Ross K
authors.initials: RK
authors.lastname: Morgan
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Thornton
authors.forename: Anthony
authors.initials: A
authors.lastname: O'Grady
authors.forename: Robert
authors.initials: R
authors.lastname: Cummins
authors.forename: Orla
authors.initials: O
authors.lastname: Sheils
authors.forename: Peter
authors.initials: P
authors.lastname: Smyth
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: Frank M
authors.initials: FM
authors.lastname: Murray
authors.forename: Richard W
authors.initials: RW
authors.lastname: Costello
mesh_terms: D001483:Base Sequence; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D017931:DNA Primers; D017615:Enteric Nervous System / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013373:Substance P / Q000378:metabolism; D016212:Transforming Growth Factor beta
chemical_list: D017931:DNA Primers; D016212:Transforming Growth Factor beta; D013373:Substance P; D002795:Choline O-Acetyltransferase