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An Activated Immune and Inflammatory Response Targets the Pancreas of Newborn Pigs with Cystic Fibrosis
Journal article   Open access   Peer reviewed

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

Maisam Abu-El-Haija, Marek Sinkora, David K Meyerholz, Michael J Welsh, Paul B McCray, John Butler and Aliye Uc
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], Vol.11(5), pp.506-515
2011
DOI: 10.1159/000332582
PMCID: PMC3224519
PMID: 22057257
url
https://doi.org/10.1159/000332582View
Published (Version of record) Open Access

Abstract

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 CFTRΔF508/ΔF508) and in those without CF (CFTR+/-, CFTR13+/ΔF508, 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+) γδ T cells, activated (MHC-II+ and/or CD25+) and effector (CD4+CD8+) αβ 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.
Flow Cytometry Lymphocytes Cystic Fibrosis Inflammation NK cells Pancreatitis Neutrophils Macrophages

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