title: Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps.
abstract: BACKGROUND
  Although chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by T(H)2 inflammation, the role of mast cells is poorly understood.
  
  
  OBJECTIVE
  The objective of this study was to investigate the presence, localization, and phenotype of mast cells in patients with CRS.
  
  
  METHODS
  We collected nasal tissue and nasal lavage fluid from patients with CRS and control subjects. We analyzed mRNA for the mast cell proteases tryptase, chymase, and carboxypeptidase A3 by using real-time PCR and measured mast cell protease proteins by using ELISA, immunohistochemistry, and immunofluorescence.
  
  
  RESULTS
  Tryptase mRNA was significantly increased in nasal polyps (NPs) from patients with CRSwNP (P< .001) compared with uncinate tissue from patients with CRS or control subjects. Tryptase protein was also elevated in NPs and in nasal lavage fluids from patients with CRSwNP. Immnohistochemistry showed increased numbers of mast cells in epithelium and glands but not within the lamina propria in NPs. The mast cells detected in the epithelium in NPs were characterized by the expression of tryptase and carboxypeptidase A3 but not chymase. Mast cells expressing all the 3 proteases were abundant within the glandular epithelium of NPs but were not found in normal glandular structures.
  
  
  CONCLUSIONS
  Herein we demonstrated a unique localization of mast cells within the glandular epithelium of NPs and showed that mast cells in NPs have distinct phenotypes that vary by tissue location. Glandular mast cells and the diverse subsets of mast cells detected may contribute to the pathogenesis of CRSwNP.
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takabayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Anju T
authors.initials: AT
authors.lastname: Peters
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Suh
authors.forename: Roderick
authors.initials: R
authors.lastname: Carter
authors.forename: James
authors.initials: J
authors.lastname: Norton
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Tan
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Chandra
authors.forename: David B
authors.initials: DB
authors.lastname: Conley
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kern
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
mesh_terms: D000293:Adolescent; D000328:Adult; D043422:Carboxypeptidases A / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D053818:Chymases / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000737:chemistry / Q000166:cytology; D009298:Nasal Polyps / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D012220:Rhinitis / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012852:Sinusitis / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053802:Tryptases / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C468648:CPA3 protein, human; D043422:Carboxypeptidases A; D053818:Chymases; D053802:Tryptases