Cell Physiol Biochem 2012;30:587-595 DOI: 10.1159/000341440 Published online: July 23, 2012 © 2012 S. Karger AG, Basel www.karger.com/cpb 587 van Barneveld/Zander/Hyde et al.: Mutant CFTR in Lung Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry 1015-8987/12/0302-0001$38.00/0 Original Paper Copyright © 2012 S. Karger AG, Basel Accepted: June 18, 2012 Klinische Forschergruppe, OE 6710 Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover (Germany) Tel. +49-511-5326722, Fax +49-511-5326723 E-Mail barneveld.andrea.van@mh-hannover.de Andrea van Barneveld Immunochemical Analysis of Mutant CFTR in Lung Explants Andrea van Barneveld a Isabell Zander b Rebecca Hyde b Florian Länger c André Simon d Marcus Krüger d Manfred Ballmann b Nico Derichs b Burkhard Tümmler a,b a Klinische Forschergruppe, OE 6710, b Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, OE 6710, c Institut für Pathologie and d Klinik für Herz-, Thorax-, Transplantations- und Gefäßchirurgie, Medizinische Hochschule Hannover, Hannover Key Words Cystic fibrosis • CFTR • Immunoblot • Lung transplantation Abstract Background/Aims: Knowledge about the abundance and distribution of CFTR protein glycoforms in native lung tissue is scarce. For upcoming studies with correctors and potentiators for CFTR it is important to get more information about mutant CFTR protein biochemistry. Target for novel treatment is the most afflicted organ in cystic fibrosis (CF), the lung. Methods: Lung tissue sampled from patients with CF and non-CF donors prior to lung transplantation was examined for CFTR-immunoreactive signals by immunoblot. Quantitation of the immunoreactive signals was carried out by densitometry. Results: The complex- glycosylated and mannose-rich CFTR isoforms were present in all non-CF specimens, whereas no or only the immature CFTR isoform was visible in CF samples. Whereas some complex- glycosylated CFTR was often present in rectal biopsies of F508del homozygous subjects, no mature CFTR was detectable in CF lungs at the stage of terminal respiratory insufficiency. Conclusion: Immunoblot analysis of CFTR in lung tissue is feasible, but in context of the upcoming studies of CFTR correctors and potentiators rectal biopsies seem to be a more appropriate choice because of their safe and repeatable excision. Introduction Cystic �ibrosis (CF) is the most common lethal disease in the Caucausian population. It is caused by mutations in the CFTR gene (OMIM 219700) which encodes a cAMP-regulated