The Effects of Varying Oxygen Conditions and Immunoglobulin A on Barrier Defense to Bacterial Invasion

Tissue oxygenation is a critical factor in host defense against bacteria. Gut mucosal tissue oxygenation (partial pressure of O2) is normally low putting the gut at risk of invasion by luminal microbes. Secretory immunoglobulin (Ig) A (sIgA) is the principal immune defense at mucosal surfaces. The protective effect of IgA under low oxygen conditions is unknown. We studied the interaction of varying O2 environments and sIgA on protection against bacterial invasion in our in vitro model. Cell monolayers of Madin-Darby canine kidney (MDCK) cells transfected with the cDNA for polymeric immunoglobulin receptor were established in a two-chamber cell culture system. A commensal strain of Escherichia coli (108 colony-forming units) was added to the apical medium and cell cultures were placed in either a 5, 21, or 95 per cent O2 environment at 37° C. Polyclonal sIgA (100 μg/mL) was added to the apical chamber in subsets. Basal medium was sampled at intervals and bacterial translocation quantitated. The cell monolayers of MDCK transfected cells then had 100 μg/mL IgA added to the basal compartment at 4° C for 2 hours followed by various oxygen environments for 90 minutes. Afterwards apical medium was removed at one, 3, and 12 (overnight) hours. The bacterial translocation data showed a significance increase in translocation with hypoxia. Both increased oxygen and IgA abrogated these effects significantly. The transcytosis of IgA was increased during hypoxic conditions. Normal and hyperoxic conditions did not produce any significant difference in IgA transcytosis. We conclude that O2 and sIgA are protective against bacterial invasion at epithelial surfaces. Effects to either boost O2 delivery to the gut or enhance mucosal IgA production and delivery may be protective in the critically ill surgical patient.