Airway expression of calcitonin gene-related peptide in T-cell peptide-induced late asthmatic reactions in atopics.
BACKGROUND
The mechanisms of late asthmatic reactions provoked in atopic asthmatics by allergen-derived T-cell peptide epitopes remain unclear. Previous studies showed no changes in airway eosinophils or mast cell products after peptide challenge. In the present study our aim was to measure calcitonin gene-related peptide (CGRP), neurokinin (NK)-A, and substance P (SP) in bronchoalveolar lavage fluid and bronchial biopsies (BB) after inhalation of allergen-derived T-cell peptide epitopes since these neuropeptides (NP) had not previously been evaluated in this chronic asthma model.


METHODS
Bronchoscopy, with BB and bronchoalveolar lavage (BAL), was performed in 24 cat-allergic subjects 6 h after inhalation of Fel d 1-derived peptides. Neuropeptides were measured in BAL by enzyme-linked immunosorbent assay and CGRP expression in the airways was assessed by immunohistochemistry and confocal microscopy.


RESULTS
Twelve subjects (termed 'responders') developed isolated late reactions. Calcitonin gene-related peptide, but not NK-A or SP, was significantly elevated in BAL in responders only. Biopsy studies showed that in virtually all responders peptide challenge induced marked increases in CGRP immunoreactivity in bronchial epithelial cells, infiltrating submucosal cells and in association with airway smooth muscle. Double immunostaining indicated that CGRP colocalized predominantly to CD3+/CD4+ and CD68+ submucosal inflammatory cells.


CONCLUSIONS
Calcitonin gene-related peptide, a potent vasodilator, is markedly up-regulated in the airways of atopic asthmatics during late-phase reactions provoked by inhalation of allergen-derived T-cell peptides.
Kay
A B
AB
Department of Allergy & Clinical Immunology, NHLI Division, Imperial College, London, UK.
Ali
F R
FR
Heaney
L G
LG
Benyahia
F
F
Soh
C P C
CP
Renz
H
H
Lee
T H
TH
Larché
M
M
D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D010455:Peptides; D015740:Calcitonin Gene-Related Peptide