Helicobacter pylori: I. Ultrastructural Sequences of Adherence, Attachment, and Penetration into the Gastric Mucosa

Abstract

New ultrastructural observations on the sequences of adherence, attachment, and penetration of Helicobacter pylori (HP) into the gastric epithelium were described in 32 endoscopic biopsies selected randomly from 168 samples of patients with active chronic gastritis. The adherence of HP to the target cell was initiated by direct contact with the microvillar coat, or glycocalyx, leading to the loss of that coat. The next step was demolishing of the surface microvilli, which separate the organisms from the cell cytoplasmic apices containing the main target of the HP, the mucoid granules. Thus the organisms come into close contact with the uncoated cell membrane and are ready for firm attachment. The attachment process was enhanced by the appearance of HP fibrillarlike strands (FLS). Up to three sites of attachment were recognized for individual organisms. Penetration into the apical cytoplasmic regions occurred by one of the organism's poles without damaging the host cell membrane. While a cell is being penetrated by one pole, FLS may extend from the other free pole to be in direct contact with the limiting membranes of the neighboring cell mucoid granules. Penetration into the gastric cells by a great number of organisms leads to serious cell damage and ultimately to cell disintegration. As a response, many neutrophils were found penetrating into the base of the gastric glands from the surrounding lamina propria; these cells were found damaged and disintegrated in the gland lumena. The neutrophils were absolutely HP-nonphagocytic. This study suggests that the dynamic activity of HP in the gastric epithelium and the possible release of the neutrophil granular contents in the gastric lumena play important roles in the gastric lesions during active chronic gastritis.

Modes of adherence of Helicobacter pylori to gastric surface epithelium in gastroduodenal disease: A possible sequence of events leading to internalisation

“…Thus, the presence of different cell adherence forms of H. pylori has been correlated with cytolysis and disintegration/destruction of the gastric epithelium (3,11,13). Another feasible indirect mechanism of action is the recruitment and activation of inflammatory cascade(s) with potent chemokines (15).…”

“…However, the results have often been discordant and in part difficult to interpret: different study models were applied, involving animal cells (14), cultured human gastric cells (9), gastric cancer cell lines (17, 21, 31), as well as tumour cell lines of other origin (18,19,22). Some investigations used live cells from patients with dyspepsia (3, 10) or gastritis (5,7,8,11,13), and only a few have included test materials from patients with gastric or duodenal ulcers (6,20). Studying adherence of H. pylori using cell lines, especially of non-gastric origin, has obvious limitations.…”

“…This was comparable to, but possibly biochemically different from, the ''attaching-effacing'' effect observed with E. coli strains carrying the eae-gene (EPEC-strains; 12,17). The specialised attachment sites on gastric cells were described as ''abutting'' (3,10), ''pedestal'' (8,11,12,24), or ''cup-like'' (8). However, some investigators failed to show such pedestal formations (4).…”

“…However, it must be noted that these investigators studied patients with dyspeptic symptoms without evidence of gastric or duodenal ulcer disease. Further studies revealed various modes of cell adhesion (3,(8)(9)(10)(11)(12) and according to some reports H. pylori was demonstrated in close proximity to parietal cells and even inside the canaliculi of resting (gastric) cells (4,8,10,13,14). …”

“…At the same time, however, Hazell et al (7) consistently observed penetration of the bacteria in the deep parts of the intercellular junctions. In contrast, many reports have demonstrated occasional (6,8,10,11,14,20,21) or frequent (12) internalisation of H. pylori in gastric mucous cells (8,10,11,14,20), parietal cells (4,14,20) or various cell lines (12,21,22). The intracellular organisms were mostly viable and sometimes associated with mucous droplets or granules (23) or vacuole spaces (22).…”