TY - JOUR
T1 - Ischaemia-induced mucus barrier loss and bacterial penetration are counteracted by increased goblet cell secretory activity in human and rat colon.
AU - Grootjans, J.
AU - Hundscheid, I.H.
AU - Lenaerts, K.
AU - Boonen, B.
AU - Renes, I.B.
AU - Verheyen, F.K.
AU - Dejong, C.H.C.
AU - von Meyenfeldt, M.F.
AU - Beets, G.L.
AU - Buurman, W.A.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - OBJECTIVE: Colonic ischaemia is frequently observed in clinical study provides a novel insight into the pathophysiology of colon ischaemia/reperfusion (IR) using a newly developed human and rat model. DESIGN: In 10 patients a small part of colon that had to be surgical reasons was isolated and exposed to 60 min of ischaemia (60I) with/without different periods of reperfusion (30R and 60R). Tissue not to IR served as control. In rats, colon was exposed to 60I, 60I/30R, 60I/240R (n=7 per group). The tissue was snap-frozen or fixed in formalin or methacarn fixative. Mucins were stained with Periodic Acid Schiff/Alcian Blue (PAS/AB) and MUC2/Dolichos biflorus agglutinin (DBA). were studied using electron microscopy (EM) and fluorescent in situ (FISH). Neutrophils were studied using myeloperoxidase staining. qPCR performed for MUC2, interleukin (IL)-6, IL-1beta and tumour necrosis alpha. RESULTS: In rats, PAS/AB and MUC2/DBA staining revealed mucus detachment at ischaemia which was accompanied by bacterial penetration FISH). Human and rat studies showed that, simultaneously, goblet cell activity increased. This was associated with expulsion of bacteria from crypts and restoration of the mucus layer at 240 min of reperfusion. was limited to minor influx of neutrophils and increased expression of proinflammatory cytokines during reperfusion. CONCLUSIONS: Colonic leads to disruption of the mucus layer facilitating bacterial is rapidly counteracted by increased secretory activity of goblet cells, to expulsion of bacteria from the crypts as well as restoration of the barrier.
AB - OBJECTIVE: Colonic ischaemia is frequently observed in clinical study provides a novel insight into the pathophysiology of colon ischaemia/reperfusion (IR) using a newly developed human and rat model. DESIGN: In 10 patients a small part of colon that had to be surgical reasons was isolated and exposed to 60 min of ischaemia (60I) with/without different periods of reperfusion (30R and 60R). Tissue not to IR served as control. In rats, colon was exposed to 60I, 60I/30R, 60I/240R (n=7 per group). The tissue was snap-frozen or fixed in formalin or methacarn fixative. Mucins were stained with Periodic Acid Schiff/Alcian Blue (PAS/AB) and MUC2/Dolichos biflorus agglutinin (DBA). were studied using electron microscopy (EM) and fluorescent in situ (FISH). Neutrophils were studied using myeloperoxidase staining. qPCR performed for MUC2, interleukin (IL)-6, IL-1beta and tumour necrosis alpha. RESULTS: In rats, PAS/AB and MUC2/DBA staining revealed mucus detachment at ischaemia which was accompanied by bacterial penetration FISH). Human and rat studies showed that, simultaneously, goblet cell activity increased. This was associated with expulsion of bacteria from crypts and restoration of the mucus layer at 240 min of reperfusion. was limited to minor influx of neutrophils and increased expression of proinflammatory cytokines during reperfusion. CONCLUSIONS: Colonic leads to disruption of the mucus layer facilitating bacterial is rapidly counteracted by increased secretory activity of goblet cells, to expulsion of bacteria from the crypts as well as restoration of the barrier.
U2 - 10.1136/gutjnl-2011-301956
DO - 10.1136/gutjnl-2011-301956
M3 - Article
C2 - 22637697
SN - 0017-5749
VL - 62
SP - 250
EP - 258
JO - Gut
JF - Gut
IS - 2
ER -