Figure 6.
Neutrophil migration and barrier integrity disruption effects by gastric fluid set at pH 3 and pH 7.4 from patients on and off PPIs. Neutrophil (PMN) migration was significantly increased across H292 lung epithelial monolayers that had been exposed to gastric fluid from patients on PPI therapy set at pH 3 compared to monolayers that had been exposed to gastric fluid from patients off PPI therapy that were set at pH 3 (A). No significant differences were observed in the magnitude of neutrophil migration induced by gastric fluid derived from patients on PPI therapy and off PPI therapy set at pH 7.4 (B). Barrier integrity disruption as measured by HRP flux was significantly increased across lung epithelial monolayers that had been exposed to gastric fluid from patients on PPI therapy versus off PPI therapy that were set at pH 3 (C), whereas no difference in magnitude of HRP flux was observed between gastric fluid samples set at pH 7.4 and derived from patients on PPI therapy or off PPI therapy (D). A dilution of 1:4 in pH matched HBSS was used for all samples. Both on and off PPI therapy groups represent the mean +/− SEM of the average magnitude values (n = 3) of PMN migration and HRP flux induced by gastric fluid derived from 12 patients on PPI therapy and 12 patients off PPI therapy, diluted 1:4 in HBSS (n = 12). Differences were considered significant between the two patient groups at p ≤ 0.05 and noted by the symbol (*). The p values were determined using an unpaired two-tailed student’s T test with equal variance within an internally controlled experiment. Panels A–D are representative internally controlled experiments conducted on at least two separate occasions yielding similar results. Supplementary Fig. S6 depicts average magnitude of neutrophil transmigration (n = 3) and Supplementary Fig. S7 depicts average magnitude of HRP flux (n = 3) induced by gastric fluid of each individual patient sample.