Expression of the anaphylatoxin receptors C3aR and C5aR is increased in fatal asthma.
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.
Fregonese
Laura
L
Department of Pulmonology, Leiden University Medical Centre, Albinusdreef 2, 2233 ZA Leiden, The Netherlands. l.fregonese@lumc.nl
Swan
Fiona J
FJ
van Schadewijk
Annemarie
A
Dolhnikoff
Marisa
M
Santos
Mario A
MA
Daha
Mohamed R
MR
Stolk
Jan
J
Tschernig
Thomas
T
Sterk
Peter J
PJ
Hiemstra
Pieter S
PS
Rabe
Klaus F
KF
Mauad
Thais
T
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
D008565:Membrane Proteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C085567:complement C3a receptor