Involvement of the immune system in phytohaemagglutinin-induced structural and functional precocious maturation of the gut in young rats

Sammanfattning: Mammals are born with an immature gastrointestinal (GI) tract that allows the uptake of the specific nutrients and bioactive macromolecules in the milk, especially the protecting maternal antibodies. Eventually during weaning, the intake of milk decreases while that of solid food increases, and the GI system undergoes prominent structural and functional changes adapting the young this dietary change. This ontogenetic development is genetically programmed but the temporal progress might be modified by dietary, gut microfloral and hormonal factors. The aim of present thesis was to investigate if a dietary component, i.e., the red kidney bean lectin phytohaemagglutinin (PHA), previously observed to be a potent inducer of GI growth in adult rats, could affect the growth and development of the immature GI tract, and to elucidate the possible mechanisms involved. The suckling rat was chosen as a model, since it is born highly immature in comparison to other mammals, and manipulation of its GI system will provide an opportunity to study the regulation of GI postnatal development in mammals. Thus, suckling rat pups at different ages, were intragastrically fed (or subcutaneously injected) with different doses of PHA either once or repeatedly during a 3-day period. The acute effects on GI structure and function were studied during the first day of PHA exposure, while the maturational effects on the GI tract were studied after 3 days. The results showed that enteral, but not parental, exposure and binding of PHA to the GI epithelium resulted in an initial transient intestinal insult, that later resulted in accelerated intestinal growth and provoked the precocious maturation of the GI system. Moreover, the effect of PHA was found to be age-related, since the GI maturational changes could only be induced after starting PHA provocation in the suckling rat from 14 days of age. The effect of PHA was also found to be dose-dependent, where low doses increased the intestinal epithelial proliferation, while high doses also induced precocious GI maturation. Taken together the results suggested that the PHA action is mediated via two pathways; one early where the lectin affects the GI mucosa by direct stimulation and there is a release of pro-inflammatory cytokines, and a later indirect pathway via transmitted signals and activation of the immune system, presumably T-cells mediated, inducing precocious GI maturation in the suckling rats. This experimental model with the dietary provocation of the suckling rat can help to increase the understanding of the postnatal developmental regulation of the GI tract, and help to design an adequate strategy for the treatment of immature neonates to improve their digestive function.

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