Ileal Immunoglobulin Binding by the Neonatal Fc Receptor: A Previously Unrecognized Mechanism of Protection in the Neonatal Rat Model of Necrotizing Enterocolitis?

Background: Mucosal apoptosis is the initiating event in models of necrotizing enterocolitis (NEC) within rodents. It is possible there are species-specific differences that make apoptosis a more prominent feature of NEC in rodents than in humans.

Hypothesis: A lower threshold for mucosal apoptosis in the rodent distal intestine might have evolutionary advantages (via enhanced opsonization with the neonatal Fc receptor [FcRn]), since many short-gestation mammals are comparatively premature (histomorphologically) but are protected from NEC by breast milk.

Methods: We utilized a rat intestinal epithelial cell (IEC-18) model to determine if cell death alters FcRn - IgG binding, and rodent models of NEC to determine if cell death results in increased opsonization of IgG. Cultured IEC-18 cells were treated with H₂O₂ and analyzed. Neonatal Sprague-Dawley rats were cold and hypoxia stressed and intestinal sections were frozen for analysis.

Results: IgG binding was increased in H₂O₂-treated cells. Co-incubation of treated cells with either insulin-like growth factor or tunicamycin decreased IgG binding. Sprague-Dawley rats formula fed with exogenous bacteria showed a significant decrease in intestinal FcRn mRNA but increased ileal IgG binding.

Conclusions: We speculate that FcRn plays a role in passive opsonization and subsequent bacterial pathogen clearance, making rodents resistant to NEC.