Level of Activation of the Unfolded Protein Response Correlates With Paneth Cell Apoptosis in Human Small Intestine Exposed to Ischemia/Reperfusion

Starvation Compromises Paneth Cells

“…30 -32 We have previously shown the additive effect of deviant Paneth cell function on the occurrence of bacterial translocation in situations of physical intestinal barrier loss. 4 These findings are in agreement with those of a previous study on Paneth cell function in vivo, in which Vaishnava et al 3 elegantly showed the crucial role of Paneth cells in limiting translocation of commensal and pathogenic bacteria across the intestinal barrier in a Paneth cell ablation model. In addition, Nieuwenhuis et al 33 associated Paneth cell granule abnormalities with alterations in the composition of the intestinal microbiota and bacteria that moved into close proximity with epithelial cells.…”

“…3 In addition, our group has recently shown the additive importance of Paneth cells in preventing bacterial translocation in situations of physical intestinal barrier loss. 4 Enteral starvation and total parenteral nutrition, as applied to critically ill patients, are reported to result in increased gut wall permeability, a compromised immune system, and bacterial translocation. [5][6][7][8][9][10] Because autophagy, a process induced on starvation, [11][12][13] influences the generation of Paneth cell granules, 14 we hypothesize that enteral starvation impairs Paneth cell function, contributing to starvation-associated gut compromise.…”

Goblet cell compound exocytosis in the defense against bacterial invasion in the colon exposed to ischemia-reperfusion

“…In addition, apoptosis of colonocytes was limited to only few cells in the crypt tips, whereas in the human small intestine IR was associated with massive apoptosis of epithelial cells in the villus tips and crypts. 17,18 Although epithelial cell damage was limited, we showed that colonic ischemia was particularly associated with damage of the mucus layer, the important first line of defense against intraluminal microbiota.…”

“…18 The epithelial lining of the human colon remained intact even after 60 min of ischemia, with or without reperfusion. In addition, apoptosis of colonocytes was limited to only few cells in the crypt tips, whereas in the human small intestine IR was associated with massive apoptosis of epithelial cells in the villus tips and crypts.…”

“…4,21 This has been described colonic IR we recently developed a human experimental colon IR model, 15 analogous to a recently developed model for human small intestinal IR. [16][17][18] The first interesting observation was that human colon tissue was far more resistant to ischemia than or cardiac bypass surgery. [9][10][11][12] In addition, intestinal hypoxia is a well-known pathophysiological phenomenon in the (chronically) inflamed mucosa, such as mucosal inflammation observed in IBD.…”