Department of Respiratory Medicine, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany
Department of Respiratory Medicine, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany
Mandy König
8sens.biognostic GmbH, Berlin, Germany
Matthias Lehmann
8sens.biognostic GmbH, Berlin, Germany
Ralf Lichtinghagen
Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
Department of Molecular Genetics, Institute of Health Carlos III, Center for Biomedical Research in the Network of Rare Diseases (CIBERER), Majadahonda, Spain
Elena Korenbaum
Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany
Department of Respiratory Medicine, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany
Nils Jedicke
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Tobias Welte
Department of Respiratory Medicine, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany
Malin Fromme
Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
Pavel Strnad
Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
Jan Stolk
Department of Pulmonology, Leiden University Medical Center, Member of European Reference Network LUNG, section Alpha-1-antitrypsin Deficiency, Leiden, Netherlands
Department of Respiratory Medicine, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany; Department of Pulmonology, Leiden University Medical Center, Member of European Reference Network LUNG, section Alpha-1-antitrypsin Deficiency, Leiden, Netherlands
Expression levels of CX3CR1 (C-X3-C motif chemokine receptor 1) on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. The factors implicated in the regulation of CX3CR1 and its specific ligand CX3CL1 (fractalkine) expression remain largely unknown. Recent studies provide evidence that host’s misfolded proteins occurring in the forms of polymers or amyloid fibrils can regulate CX3CR1 expression. Herein, a novel example demonstrates that polymers of human ZZ alpha-1 antitrypsin (Z-AAT) protein, resulting from its conformational misfolding due to the Z (Glu342Lys) mutation in SERPINA1 gene, strongly lower CX3CR1 mRNA expression in human peripheral blood mononuclear cells (PBMCs). This parallels with increase of intracellular levels of CX3CR1 and Z-AAT proteins. Presented data indicate the involvement of the CX3CR1 pathway in the Z-AAT-related disorders and further support the role of misfolded proteins in CX3CR1 regulation.
