title: S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity.
abstract: BACKGROUND
  The calcium-binding protein S100A12 might provoke inflammation and monocyte recruitment through the receptor for advanced glycation end products.
  
  
  OBJECTIVE
  Because inflammation elicited by S100A12 in vivo had characteristics of mast cell (MC) activation, we aimed to define the mechanism.
  
  
  METHODS
  Various MC populations were used to test S100A12 activation assessed on the basis of morphology, histamine release, leukotriene production, and cytokine induction. MC dependence of S100A12-provoked inflammation was tested in mice and on the rat microcirculation by means of intravital microscopy. Immunohistochemistry localized S100A12 in the asthmatic lung, and levels in sputum from asthmatic patients were quantitated by means of ELISA. Expression of the receptor for advanced glycation end products was evaluated by means of RT-PCR and Western blotting.
  
  
  RESULTS
  S100A12 provoked degranulation of mucosal and tissue MCs in vitro and in vivo and amplified IgE-mediated responses. It induced a cytokine profile indicating a role in innate/T(H)1-mediated responses. S100A12-induced edema and leukocyte rolling, adhesion, and transmigration in the microcirculation were MC dependent. Eosinophils in airway tissue from asthmatic patients were S100A12 positive, and levels were increased in sputum. S100A12 responses were partially blocked by an antagonist to the receptor for advanced glycation end products, but MCs did not express mRNA or protein, suggesting an alternate receptor.
  
  
  CONCLUSIONS
  This novel pathway highlights the potential importance of S100A12 in allergic responses and in infectious and chronic inflammatory diseases.
  
  
  CONCLUSIONS
  MC activation by S100A12 might exacerbate allergic inflammation and asthma. S100A12 might provide a novel marker for eosinophilic asthma.
authors.affiliation: School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.forename: Wei Xing
authors.initials: WX
authors.lastname: Yan
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.forename: Nicodemus
authors.initials: N
authors.lastname: Tedla
authors.forename: Chris
authors.initials: C
authors.lastname: Armishaw
authors.forename: Nick
authors.initials: N
authors.lastname: Di Girolamo
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Taline
authors.initials: T
authors.lastname: Hampartzoumian
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Simpson
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
authors.forename: John
authors.initials: J
authors.lastname: Hunt
authors.forename: Prue
authors.initials: P
authors.lastname: Hart
authors.forename: J Margaret
authors.initials: JM
authors.lastname: Hughes
authors.forename: Michael A
authors.initials: MA
authors.lastname: Perry
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Geczy
mesh_terms: D000328:Adult; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001987:Bronchiectasis / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000494:pharmacology*; D000067616:S100A12 Protein; D013183:Sputum / Q000737:chemistry
chemical_list: D016207:Cytokines; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human