Mucosal macrophage inflammatory protein‐1α activity in Helicobacter pylori infection

Abstract

Mucosal chemokines are considered to be important in the pathogenesis of Helicobacter pylori-associated gastritis. The aims of this study are to examine the levels of macrophage inflammatory protein-1α (MIP-1α) in organ cultures, the expression of MIP-1α mRNA and the cellular source of MIP-1α, using the antral mucosal specimens obtained from H. pylori-positive and -negative patients. Enzyme-linked immunosorbent assay was used to measure the levels of MIP-1α in organ cultures of mucosal tissues and cell cultures of fractionated mucosal cells. The expression of MIP-1α mRNA and protein was analysed in fresh biopsy tissues with reverse transcriptase–polymerase chain reaction (RT-PCR) and double immunofluorescence microscopy, respectively. The mucosal specimens obtained from H. pylori-positive patients exhibited significantly higher values of MIP-1α activity in organ cultures with increased numbers of CD68⁺ macrophages, myeloperoxidase⁺ neutrophils and mononuclear cells in the lamina propria compared with those from H. pylori-negative patients. The RT-PCR analysis detected MIP-1α mRNA in more than 50% of the specimens with H. pylori infection, but not in those without infection. In cell cultures, the macrophage fraction contained substantially higher amounts of MIP-1α on a per cell basis than the lymphocyte fraction and MIP-1α activity was not detected in cultures of gastric epithelial cells. This observation was also confirmed by a double immunofluorescence microscopic study in which most (> 90%) MIP-1α-positive infiltrating cells were CD68⁺ macrophages. This study indicates that synthesis and secretion of MIP-1α are increased in H. pylori-infected antral mucosa and that mucosal macrophages are the main cell type responsible for this phenomenon.