An activated immune and inflammatory response targets the pancreas of newborn pigs with cystic fibrosis.

نویسندگان

  • Maisam Abu-El-Haija
  • Marek Sinkora
  • David K Meyerholz
  • Michael J Welsh
  • Paul B McCray
  • John Butler
  • Aliye Uc
چکیده

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(Δ)(F508/)(Δ)(F508)) and in those without CF (CFTR(+/-), CFTR(+/)(Δ)(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(+)) 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.

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عنوان ژورنال:
  • Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]

دوره 11 5  شماره 

صفحات  -

تاریخ انتشار 2011