Helicobacter pylori-associated gastritis is mainly an inflammatory cell response. In earlier work we showed that activation of human neutrophils by a cell-free water extract of H. pylori is characterized by increased expression of neutrophil CD11b/CD18 and increased adhesiveness to endothelial cells. The work reported here indicates that the neutrophil-activating factor is a 150,000-molecular-weight protein (150K protein). Neutrophil proadhesive activity copurified with this protein, which is a polymer of identical 15K subunits. Specific antibody, prepared against the purified 15K subunit, neutralized the proadhesive activity of the pure protein and of water extracts obtained from different strains of H. pylori. The gene (napA) for this protein (termed HP-NAP, for H. pylori neutrophil-activating protein) was detected, by PCR amplification, in all of the H. pylori isolates tested; however, there was considerable strain variation in the level of expression of HP-NAP activity in vitro. HP-NAP could play an important role in the gastric inflammatory response to H. pylori infection. Helicobacter pylori is closely associated with gastric and peptic ulcer disease and with the development of duodenal ulcers (9, 21, 22, 39, 51). Chronic H. pylori gastritis is also a major risk factor for development of gastric cancer (8, 27, 44, 54). H. pylori infection elicits an inflammatory cell response, and the severity of mucosal injury appears to be directly correlated with the extent of neutrophil infiltration (9, 11, 13, 14, 18, 22, 32, 37, 38). It has been suggested that activated leukocytes may be responsible for some of the tissue damage seen in cases of H. pylori gastritis (5, 13, 14, 22, 35, 42) and that activated phagocytes, especially in the presence of H. pylori products, contribute to carcinogenesis (53, 55). Since the primary consequence of H. pylori infection is gastritis, many investigations have centered on the mechanisms involved in the gastric inflammatory response (
