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Platelet-derived growth factor (PDGF)-BB regulates the airway tone via activation of MAP2K, thromboxane, actin polymerisation and Ca2+-sensitisation.
Rieg, Annette D; Suleiman, Said; Anker, Carolin; Bünting, Nina A; Verjans, Eva; Spillner, Jan; Kalverkamp, Sebastian; von Stillfried, Saskia; Braunschweig, Till; Uhlig, Stefan; Martin, Christian.
Afiliación
  • Rieg AD; Department of Anaesthesiology, Medical Faculty RWTH-Aachen, Aachen, Germany. arieg@ukaachen.de.
  • Suleiman S; Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, Aachen, Germany.
  • Anker C; Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, Aachen, Germany.
  • Bünting NA; Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, Aachen, Germany.
  • Verjans E; Department of Paediatrics, Medical Faculty RWTH-Aachen, Aachen, Germany.
  • Spillner J; Department of Cardiac and Thorax Surgery, Medical Faculty RWTH-Aachen, Aachen, Germany.
  • Kalverkamp S; Department of Cardiac and Thorax Surgery, Medical Faculty RWTH-Aachen, Aachen, Germany.
  • von Stillfried S; Institute of Pathology, Medical Faculty RWTH-Aachen, Aachen, Germany.
  • Braunschweig T; Institute of Pathology, Medical Faculty RWTH-Aachen, Aachen, Germany.
  • Uhlig S; Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, Aachen, Germany.
  • Martin C; Institute of Pharmacology and Toxicology, Medical Faculty RWTH-Aachen, Aachen, Germany.
Respir Res ; 23(1): 189, 2022 Jul 15.
Article en En | MEDLINE | ID: mdl-35841089
BACKGROUND: PDGFR-inhibition by the tyrosine kinase inhibitor (TKI) nintedanib attenuates the progress of idiopathic pulmonary fibrosis (IPF). However, the effects of PDGF-BB on the airway tone are almost unknown. We studied this issue and the mechanisms beyond, using isolated perfused lungs (IPL) of guinea pigs (GPs) and precision-cut lung slices (PCLS) of GPs and humans. METHODS: IPL: PDGF-BB was perfused after or without pre-treatment with the TKI imatinib (perfused/nebulised) and its effects on the tidal volume (TV), the dynamic compliance (Cdyn) and the resistance were studied. PCLS (GP): The bronchoconstrictive effects of PDGF-BB and the mechanisms beyond were evaluated. PCLS (human): The bronchoconstrictive effects of PDGF-BB and the bronchorelaxant effects of imatinib were studied. All changes of the airway tone were measured by videomicroscopy and indicated as changes of the initial airway area. RESULTS: PCLS (GP/human): PDGF-BB lead to a contraction of airways. IPL: PDGF-BB decreased TV and Cdyn, whereas the resistance did not increase significantly. In both models, inhibition of PDGFR-(ß) (imatinib/SU6668) prevented the bronchoconstrictive effect of PDGF-BB. The mechanisms beyond PDGF-BB-induced bronchoconstriction include activation of MAP2K and TP-receptors, actin polymerisation and Ca2+-sensitisation, whereas the increase of Ca2+ itself and the activation of EP1-4-receptors were not of relevance. In addition, imatinib relaxed pre-constricted human airways. CONCLUSIONS: PDGFR regulates the airway tone. In PCLS from GPs, this regulatory mechanism depends on the ß-subunit. Hence, PDGFR-inhibition may not only represent a target to improve chronic airway disease such as IPF, but may also provide acute bronchodilation in asthma. Since asthma therapy uses topical application. This is even more relevant, as nebulisation of imatinib also appears to be effective.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Actinas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Respir Res Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Actinas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Respir Res Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido