Background: Gut ischemia may prime neutrophils to produce an exaggerated inflammatory response when challenged with bacterial pathogens. Secretory immunoglobulin A (sIgA) is the first line of defense against potential pathogens, but may also exert its anti-inflammatory effects on potentially destructive neutrophil functions. We hypothesized that sIgA would blunt the gut-mediated priming events that lead to neutrophil hypersensitivity to bacterial challenge.
Methods: Confluent Caco2 cell monolayers were grown in a two-chamber culture system under normoxic or hypoxic conditions for 90 minutes followed by a 90-minute reoxygenation period. sIgA was placed in apical chamber media in experimental groups before reoxygenation period. Supernatants were then collected and incubated with neutrophils. Lipopolysaccharide was then used to activate neutrophils. Measurements of CD11b expression, elastase and superoxide anion production, and chemotaxis were undertaken.
Results: Polymorphonuclear neutrophils (PMNs) treated with Caco2 cells undergoing hypox-reoxygenation followed by activation with lipopolysaccharide show a dramatic increase in inflammatory potential when compared with naïve neutrophils (n = 4, *p < 0.001). The addition of sIgA in this same group before the activation step showed a blunting of the inflammatory response, but never to the level of naïve PMN.
Conclusions: sIgA is the principal defense against potential pathogens at mucosal surfaces. Additional protective activity may be found in its ability to downregulate gut-mediated neutrophil priming. Although more work needs to be performed examining the role of sIgA in the pathogenesis of sepsis, this study shows that sIgA downregulates the measured determinants of neutrophil inflammatory potential.