title: Mast cells express IL-13R alpha 1: IL-13 promotes human lung mast cell proliferation and Fc epsilon RI expression.
abstract: BACKGROUND
  The Th2 cytokine interleukin (IL)-13 is implicated in the development of various allergic diseases including asthma. The IL-13 receptor, IL-13Ralpha1, is expressed on most leukocytes, except T-cells. Evidence to support IL-13Ralpha1 expression on mast cells is limited.
  
  
  METHODS
  We investigated: (i) IL-13Ralpha1 expression by human lung mast cells (HLMC); (ii) the number of IL-13Ralpha1+ bronchial submucosal mast cells in subjects with asthma and normal controls and (iii) the effect of IL-13 priming on HLMC expression of high-affinity IgE receptor (FcepsilonRI), stem cell factor receptor (CD117), histamine release, proliferation, and survival.
  
  
  RESULTS
  Human lung mast cell expressed IL-13Ralpha1 mRNA. IL-13Ralpha1 was highly expressed on the surface HLMC (82+/-9%). Bronchial submucosal mast cell IL-13Ralpha1 expression was higher in asthmatics (86+/-2%) than normal controls (78+/-2%; P=0.015). IL-13 priming for 30 min did not increase HLMC histamine release, in the presence or absence of SCF or in response to IgE/anti-IgE activation. IL-13 priming for 5 days upregulated HLMC FcepsilonRI expression (22% increase in fluorescent intensity; P=0.003), increased histamine release following IgE/anti-IgE activation by 56% (P=0.03) and increased proliferation by 50% (P=0.003) without affecting cell survival or CD117 expression. The IL-13 specific neutralizing antibody CAT-354 inhibited all IL-13 mediated effects.
  
  
  CONCLUSIONS
  Human lung mast cell express IL-13Ralpha1 and activation by IL-13 for 5 days increased FcepsilonRI expression and proliferation. Histamine release was not affected by short-term priming with IL-13, but was upregulated by priming for 5 days suggesting that this effect was mediated by the increased FcepsilonRI expression. These data support the view that targeting IL-13 may be beneficial in the treatment of asthma.
authors.affiliation: Department of Infection, Institute for Lung Health, Inflammation and Immunity, University of Leicester, Leicester, UK.
authors.forename: D
authors.initials: D
authors.lastname: Kaur
authors.forename: F
authors.initials: F
authors.lastname: Hollins
authors.forename: L
authors.initials: L
authors.lastname: Woodman
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: P
authors.initials: P
authors.lastname: Monk
authors.forename: R
authors.initials: R
authors.lastname: May
authors.forename: P
authors.initials: P
authors.lastname: Bradding
authors.forename: C E
authors.initials: CE
authors.lastname: Brightling
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D018793:Interleukin-13 / Q000502:physiology*; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000096:biosynthesis / Q000235:genetics*; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D017455:Receptors, IgE / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D017455:Receptors, IgE