Mast cells infiltrate the esophageal smooth muscle in patients with eosinophilic esophagitis, express TGF-β1, and increase esophageal smooth muscle contraction.
BACKGROUND
Increased numbers of mast cells are present in the esophageal epithelium in patients with eosinophilic esophagitis (EE). However, mast cell infiltration into the esophageal lamina propria (LP) and smooth muscle (SM) and the effects of their products on SM function has not been determined.


OBJECTIVE
We investigated mast cell localization and characterization in esophageal SM, the functional significance of mast cell TGF-β1 expression to contraction of human esophageal smooth muscle (HESM) cells in vitro, and the effect of topical corticosteroids on the number of tryptase-positive (MC(T)) and chymase-positive (MC(C)) mast cells in patients with EE.


METHODS
MC(T)- and MC(C)-positive mast cell numbers were quantitated in the epithelium, the LP before and after topical corticosteroid therapy, and the muscularis mucosa in patients with EE and control subjects by using immunohistology. Double immunofluorescence was used to assess mast cell production of TGF-β1. The ability of TGF-β1 to influence HESM cell contractility was assessed in vitro.


RESULTS
In the SM in patients with EE, significantly increased numbers of MC(T)- and TGF-β1-positive cells (but only low levels of eosinophils) were detected compared with those seen in control subjects. MC(T) expressed TGF-β1, which increased the contractility of cultured primary HESM cells in vitro. Topical corticosteroid therapy in patients with EE significantly reduced epithelial MC(T) numbers but not LP tryptase-chymase-positive mast cell numbers.


CONCLUSIONS
MC(T) numbers, rather than eosinophil numbers, are increased in the SM in patients with EE, express TGF-β1, and increase the contractility of HESM cells in vitro. As such, mast cells localized to SM in patients with EE might modulate esophageal contractility.
Division of Allergy and Immunology, University of California and Rady Children's Hospital, San Diego, USA. saceves@ucsd.edu
Seema S
SS
Aceves
Diana
D
Chen
Robert O
RO
Newbury
Ranjan
R
Dohil
John F
JF
Bastian
David H
DH
Broide
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D053818:Chymases / Q000096:biosynthesis; D057765:Eosinophilic Esophagitis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009092:Mucous Membrane / Q000473:pathology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053802:Tryptases / Q000096:biosynthesis
D000305:Adrenal Cortex Hormones; D053773:Transforming Growth Factor beta1; D053818:Chymases; D053802:Tryptases