PURPOSE: Helicobacter pylori (H.pylori), a well-known gastric pathogen causing gastritis and esophageal reflux, may be introduced to the airways through aspiration. Recent case-control studies correlate bronchiectasis, chronic bronchitis and other pulmonary pathologies with H.pylori infection. About 12% of H. pylori protein is urease, which converts host urea in the gastric environment. We have shown that low-level intratracheal urease upregulates peribronchial nodes in experimental animals. This study tests the hypothesis: intratracheal urease pretreatment will upregulate the immune response to H. pylori protein-coated beads in the lung compared to saline pretreatment.
METHODS: Rats were pretreated for 3 weeks with 0.05 units urease or sterile saline intratracheally (n=10 each group). Primary amino groups of purified H. pylori protein were bound to activated CH-sepharose beads. Control beads were unlabeled. Animals were administered 3000 beads in 0.5 mL saline intravenously in the tail vein. Lungs were harvested on days 1, 7, and 14. CD3, CD68, CD79a and H&E staining were evaluated by a pulmonary pathologist.
RESULTS: Microscopic counts were made of T and B cells surrounding 25 beads in each lung. Inflammation was exhibited around most beads. Mean T cell count (25 beads) ranged from 147 on day 1 to 494 on day 7, higher with urease pretreatment p=0.007. B cells (CD79) ranged from 5 on day 1 to 644 on day 7, a significant increase with urease but not saline pretreatment, p=0.05. Granuloma formation (CD68 cells) around Hp-coated beads was elevated at 14 days in urease rats but did not reach significance.
CONCLUSION: At 7 days, inflammation and bead-related granulomas related to pretreatment (urease or saline) suggesting that urease pretreatment upregulates cellular response to H. pylori protein-coated beads in the lung. The data offer more evidence that H. pylori gastric infection has potential to influence lung inflammation and potentially the formation of granulomas.
CLINICAL IMPLICATIONS: This is an interesting view on the formation of granulomas in patient with H.pylori. Perhaps treating/testing for H.pylori in patients with sarcoidosis would improve symptoms.
DISCLOSURE: Wessam Yacoub, No Financial Disclosure Information; No Product/Research Disclosure Information