The mucosal immune system is relevant for homeostasis, immunity, and also pathology in the gastrointestinal tract. Inducible nitric oxide synthase (iNOS) dependent production of nitric oxide (NO) is one of the factors linked to both anti-microbial immunity and pathology. Up-regulation of iNOS has been observed in human Helicobacter pylori infection, the major cause of gastric ulcer, adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma, but the cellular sources of iNOS and NO are ill defined.
Methods:
To characterize mucosal iNOS-producing leukocyte subtypes in H. pylori-infected patients, antral biopsy specimens from 41 H. pylori-infected patients and 24 H. pylori-negative controls were analyzed by immunohistochemistry, along with flow cytometric analyses of isolated lymphocytes for iNOS expression and activity. Additionally, 24 biopsy specimens from a vaccination trial were analyzed immunohistochemically.
Results:
Besides macrophages, we newly identified mucosal IgA-expressing plasma cells (PCs) as one major iNOS+ cell population detected in H. pylori-infected patients. Since we did not detect iNOS+ PCs in four distinct infectious diseases, this finding is not a general feature of mucosal PCs under conditions of infection. By flow cytometry intracellular NO production was detected in live PCs. Furthermore, numbers of iNOS+ PCs were elevated in the mucosa of individuals who had cleared experimental H. pylori infection compared to those who had not.
Conclusion:
IgA+ PCs expressing iNOS are described for the first time in humans. iNOS+ PCs are induced in the course of human H. pylori infection and may contribute to the clinical course of the infection.