Monocyte derived macrophages from CF pigs exhibit increased inflammatory responses at birth

• Published in: Journal of cystic fibrosis Vol. 16; no. 4; pp. 471 - 474
• Main Authors: Paemka, Lily, McCullagh, Brian N, Abou Alaiwa, Mahmoud H, Stoltz, David A, Dong, Qian, Randak, Christoph O, Gray, Robert D, McCray, Paul B
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2017; Elsevier
• Subjects: Animals; Animals, Newborn; CFTR; Cystic Fibrosis - genetics; Cystic Fibrosis - immunology; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Disease Models, Animal; Immunization - methods; Inflammation; Inflammation - immunology; Interleukin-8 - analysis; Lipopolysaccharide; Lipopolysaccharides - immunology; Macrophage; Macrophages - immunology; Monocyte; Patch-Clamp Techniques - methods; Pulmonary/Respiratory; Swine; Tumor Necrosis Factor-alpha - analysis; Lipopolysaccharide; Inflammation; Monocyte; CFTR; Macrophage
• ISSN: 1569-1993; 1873-5010
• DOI: 10.1016/j.jcf.2017.03.007

Abstract Background We sought to address whether CF macrophages have a primary functional defect as a consequence of CFTR loss and thus contribute to the onset of infection and inflammation observed in CF lung disease. Methods Monocyte derived macrophages (MDMs) were prepared from newborn CF and non-CF pigs . CFTR mRNA expression was quantified by rtPCR and anion channel function was determined using whole cell patch clamp analysis. IL8 and TNFα release from MDMs in response to lipopolysaccharide stimulation was measured by ELISA. Results CFTR was expressed in MDMs by Q-rtPCR at a lower level than in epithelial cells. MDMs exhibited functional CFTR current at the cell membrane and this current was absent in CF MDMs. CF MDMs demonstrated an exaggerated response to lipopolysaccharide stimulation. Conclusions In the absence of CFTR function, macrophages from newborn CF pigs exhibit an increased inflammatory response to a lipopolysaccharide challenge. This may contribute to the onset and progression of CF lung disease.