title: Expression of the anaphylatoxin receptors C3aR and C5aR is increased in fatal asthma.
abstract: BACKGROUND
  The mechanisms leading to death from asthma are not completely understood. Recent studies suggest the involvement of the anaphylatoxins C3a and C5a, generated during complement activation, and their receptors C3aR and C5aR in the pathogenesis of asthma.
  
  
  OBJECTIVE
  The aim of our study was to investigate the expression of C3aR and C5aR in fatal asthma.
  
  
  METHODS
  We analyzed lung tissue from 14 subjects who died of asthma (fatal asthma; FA) and 14 subjects who died of nonpulmonary causes (controls) and bronchial biopsy specimens from 16 subjects with mild intermittent asthma (MIA). C3aR and C5aR expression was evaluated by immunohistochemistry, and a semiquantitative analysis of the intensity of staining was performed according to a visual analogue scale (score, 0-3).
  
  
  RESULTS
  C3aR was expressed on airway epithelium, smooth muscle, submucosal, and parenchymal vessels. C5aR was expressed on myeloid cells infiltrating the submucosa and on airway epithelium. Statistical analysis demonstrated higher expression of C3aR on submucosal vessels in FA compared with controls and MIA (median [minimum-maximum], controls, 0.24 [0-1.48]; MIA, 0.0 [0-1.00]; FA, 1.56 [0.13-3]; P = .002). C3aR was also increased on parenchymal vessels in FA (controls, 0.56 [0-2.00]; FA, 1.81 [0.5-3]; P = .0004). C5aR expression on airway epithelium was increased in FA compared with controls and MIA (controls, 1.25 [0.25-3]; MIA, 1.00 [0-2.00]; FA, 3.00 [1.13-3.00]; P = .001).
  
  
  CONCLUSIONS
  The results of our study suggest a role of complement in FA.
authors.affiliation: Department of Pulmonology, Leiden University Medical Centre, Albinusdreef 2, 2233 ZA Leiden, The Netherlands. l.fregonese@lumc.nl
authors.forename: Laura
authors.initials: L
authors.lastname: Fregonese
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Swan
authors.forename: Annemarie
authors.initials: A
authors.lastname: van Schadewijk
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolhnikoff
authors.forename: Mario A
authors.initials: MA
authors.lastname: Santos
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: Jan
authors.initials: J
authors.lastname: Stolk
authors.forename: Thomas
authors.initials: T
authors.lastname: Tschernig
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Rabe
authors.forename: Thais
authors.initials: T
authors.lastname: Mauad
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000473:pathology*; D001344:Autopsy; D001706:Biopsy; D003167:Complement Activation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D044087:Receptor, Anaphylatoxin C5a / Q000032:analysis*; D011951:Receptors, Complement / Q000032:analysis*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C085567:complement C3a receptor