Effect of the lectin concanavalin A on the neonatal guinea pig gastrointestinal mucosa in vivo.
The effect of intrapharyngeal infusion and subsequent passage of the lectin concanavalin A through the gastrointestinal tract of neonatal guinea pigs was examined. The lectin, administered at a concentration of 1 mg/ml, caused considerable mucosal damage in the stomach. Subsequent passage of the lectin through the small intestine caused little cellular damage to the mucosa, as judged by light and electron microscopy. Parallel morphometric analyses of the jejunum showed a decrease in mean villus height and an increase in mean crypt depth of 8% after 5 h of lectin administration. A 4.7-fold increase in jejunal crypt cell production rate was observed, accompanied by a statistically significant increase in the number of intraepithelial lymphocytes. These morphologic and kinetic changes were accompanied by a three-fold increase in the urinary lactulose:mannitol excretion ratio, indicative of a loss of mucosal integrity. No systemic antibody response to concanavalin A was demonstrated within 5 h of intragastric infusion of the lectin. Concanavalin A, conjugated with 10 nm colloidal gold particles, was also directly infused into the lumen of the jejunum in vivo. Within 60 min, both villous and crypt epithelial cells contained gold particles, demonstrating the rapid accessibility of crypt cells to the lectin. Intercellular spaces appeared within the villous epithelium, although both junctional complexes and spot desmosomes were retained. The brush border was abnormal with signs of incipient vesicularization. These findings have implications for our understanding of the pathogenesis of childhood coeliac disease and for the vulnerability of the neonatal gut to food proteins.
MRC Dunn Nutritional Laboratory, University of Cambridge, England.
L T
LT
Weaver
D S
DS
Bailey
D000818:Animals; D000831:Animals, Newborn; D002463:Cell Membrane Permeability / Q000187:drug effects; D003208:Concanavalin A / Q000378:metabolism / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects; D006168:Guinea Pigs; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects*; D008854:Microscopy, Electron; D011952:Receptors, Concanavalin A / Q000378:metabolism
D011952:Receptors, Concanavalin A; D003208:Concanavalin A