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. 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.
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. 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.
Authors: Gandhi F Pavón-Romero; Nancy Haydée Serrano-Pérez; Lizbeth García-Sánchez; Fernando Ramírez-Jiménez; Luis M Terán Journal: Front Cell Dev Biol Date: 2021-05-13
Authors: Alessia Balestrini; Victory Joseph; Michelle Dourado; Rebecca M Reese; Shannon D Shields; Lionel Rougé; Daniel D Bravo; Tania Chernov-Rogan; Cary D Austin; Huifen Chen; Lan Wang; Elisia Villemure; Daniel G M Shore; Vishal A Verma; Baihua Hu; Yong Chen; Laurie Leong; Chris Bjornson; Kathy Hötzel; Alvin Gogineni; Wyne P Lee; Eric Suto; Xiumin Wu; John Liu; Juan Zhang; Vineela Gandham; Jianyong Wang; Jian Payandeh; Claudio Ciferri; Alberto Estevez; Christopher P Arthur; Jens Kortmann; Ryan L Wong; Jose E Heredia; Jonas Doerr; Min Jung; Jason A Vander Heiden; Merone Roose-Girma; Lucinda Tam; Kai H Barck; Richard A D Carano; Han Ting Ding; Bobby Brillantes; Christine Tam; Xiaoying Yang; Simon S Gao; Justin Q Ly; Liling Liu; Liuxi Chen; Bianca M Liederer; Joseph H Lin; Steven Magnuson; Jun Chen; David H Hackos; Justin Elstrott; Alexis Rohou; Brian S Safina; Matthew Volgraf; Rebecca N Bauer; Lorena Riol-Blanco Journal: J Exp Med Date: 2021-04-05 Impact factor: 14.307
Authors: Manyu Li; Sarah E Wetzel-Strong; Xiaoyang Hua; Stephen L Tilley; Erin Oswald; Matthew F Krummel; Kathleen M Caron Journal: PLoS One Date: 2014-07-10 Impact factor: 3.240