Studies of intestinal lymphoid tissue. XII. Epithelial lymphocyte and mucosal responses to rectal challenge in celiac sprue

Department of Medicine, University of Manchester School of Medicine, United Kingdom.
Gastroenterology (Impact Factor: 16.72). 08/1989; 97(1):29-37.
Source: PubMed


The immunopathologic, structural, and functional changes within rectal mucosa of known celiac sprue subjects were quantitated during local challenge with a peptic-tryptic digest of gluten. In the celiac sprue patients challenged with 2 g of digest, major effects occurred in lamina propria, submucosa, and local microvasculature. The lamina propria swelling was biphasic, starting 1-2 h after challenge with widespread extravascular deposition of fibrinogen, indicative of increased microvascular permeability, receding by 24 h postchallenge. A rapid fall in mast cells together with granule discharge suggested their involvement in this response. The late-phase swelling (48-72 h) was preceded by a rapid influx of neutrophils and basophils, the latter showing evidence of degranulation beyond 72 h. Reestablishment of vessel lumina, a rise in mast cells, and loss of neutrophils indicated tapering of the inflammatory cellular cascade by 96 h. Lymphocytes, first seen to enter the lamina by 2 h postchallenge, increased progressively, thereby resulting in substantial infiltration between 36 and 96 h. A marked rise in epithelial lymphocytes, maximal at 6-8 h, waned by 24 h. Volumes of surface and crypt epithelium remained constant throughout. In another challenge series with 4 g of gluten digest, electrical potential difference across rectal mucosa decreased significantly 12 h postchallenge, but the associated decreases in net sodium and chloride absorptive fluxes were insignificant. It is concluded that rectal mucosa is sensitized to gluten in celiac sprue disease and thus offers a promising and convenient in vivo substrate for investigative and diagnostic purposes.

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    • "However, small bowel biopsy from patients with isolated CD or in CD associated with DH shows that neutrophils are not the predominant cells; it is possible that neutrophils represent the earliest inflammatory cell, but the continued stimulation with gluten results in a transition to the more typical mononuclear cell infiltrate. Confirming this hypothesis, it has been demonstrated a pronounced neutrophilic activation in CD after rectal gluten challenge in the first 4–6 hours [76, 77]. "
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    • "IL-8 is a potent neutrophil chemokine, however, neutrophils are not prominently noted in the small bowel biopsies of patients with isolated GSE or in the GSE associated with DH. It is of interest that in time course studies carried out after gluten challenges in the rectum of patients with isolated GSE, neutrophils were most prominently present in the first 4–6 hours (Loft et al., 1989; Kristjansson et al., 2005). This finding suggests that neutrophils may represent an early event after initial gluten challenge. "
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