Airway Expression of Calcitonin Gene-Related Peptide in T-Cell Peptide-Induced Late Asthmatic Reactions

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 generelated peptide (CGRP), neurokinin (NK)-A, and substance P (SP) in bronchoalveolar lavage fluid and bronchial biopsies (BB) after inhalation of allergenderived 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. Conclusion: 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.