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

Lily Paemka, Brian N. McCullagh, Mahmoud H. Abou Alaiwa, David A. Stoltz, Qian Dong, Christoph O. Randak, Robert D. Gray, Paul B. McCray

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)471-474
Number of pages4
JournalJournal of Cystic Fibrosis
Volume16
Issue number4
DOIs
Publication statusPublished - Jul 2017
Externally publishedYes

Keywords

  • CFTR
  • Inflammation
  • Lipopolysaccharide
  • Macrophage
  • Monocyte

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