An Activated Immune and Inflammatory Response Targets the Pancreas of Newborn Pigs with Cystic Fibrosis

作者：Abu El Haija Maisam; Sinkora Marek; Meyerholz David K; Welsh Michael J; McCray Paul B Jr; Butler John; Uc Aliye^*

来源：Pancreatology, 2011, 11(5): 506-515.

DOI：10.1159/000332582

• Cystic fibrosis
• Pancreatitis
• Flow cytometry
• Inflammation
• Lymphocytes
• Neutrophils
• Macrophages
• NK cells

Background/Aims: In cystic fibrosis (CF), pancreatic disease begins in utero and progresses over time to complete destruction of the organ. Although inflammatory cells have been detected in the pancreas of humans and pigs with CF, their subtypes have not been characterized. Methods: Using four-color flow cytometry, we analyzed the surface antigens of leukocytes in pancreas, blood, and mesenteric lymph nodes (MLN) of newborn pigs with CF (CFTR(-/-) and CFTR(Delta F508/Delta F508)) and in those without CF (CFTR(+/-), CFTR(+/Delta F508), CFTR(+/+)). Pancreatic histopathology was examined with HE stain. Results: CF pig pancreas had patchy distribution of inflammatory cells with neutrophils/macrophages in dilated acini, and lymphocytes in the interstitium compared to non-CF. B cells, effector (MHC-II(+)) and cytotoxic (CD2(+)CD8(+) ) gamma delta T cells, activated (MHC-II(+) and/or CD25(+)) and effector (CD4(+)CD8(+)) alpha beta T helper cells, effector natural killer cells (MHC-II(+)CD3(-)CD8(+)), and monocytes/macrophages and neutrophils were increased in the CF pig pancreas compared to pigs without CF. Blood and MLN leukocyte populations were not different between CF and non-CF pigs. Conclusions: We discovered an activated immune response that was specific to the pancreas of newborn CF pigs; inflammation was not systemic. The presence of both innate and adaptive immune cells suggests that the disease process is complex and extensive.

• 出版日期2011