Recovery from gastric mucus depletion in the intact guinea pig mucosa.

BACKGROUND: In developed countries one-third of the population is infected with the gastric pathogen Helicobacter pylori. In the early stages of H. pylori-induced gastritis, typical symptoms include gastric erosions and mucus depletions. Artificial mucus depletion was generated, demonstrating both consequent irritation and recovery processes in the mucosa. METHODS: The mucus depletion was examined by removing a small cylinder of mucus from the surface of the explanted guinea pig corpus mucosa, leaving the epithelial surface intact. pH microelectrodes were inserted into the mucosa in vitro, measuring the epicellular mucus pH, the pH(i) of the underlying epithelial cells and the pH inside the gastric glands during mucus regeneration. Using infrared microscopy, the same process of mucus layer renewal was followed in anaesthetized animals. RESULTS: The depletion exposed the tissue surface to low luminal pH levels. At a luminal pH of 2.5, a decrease was observed in the crypt outlet pH and surface cell pH(i), while deeper cells were less affected. However, a subsequent neutralization in the deep gland lumen was found. During the repair process, a quarter of the mucus layer was regenerated within the first 5 min. This newly secreted mucus formed a structure similar to that before depletion. Within 45 min, pH(i) and tissue-near pH values had fully recovered. CONCLUSION: Following mucus depletion, there is a decrease in surface cell pH(i) and crypt outlet pH values. The repair process is then characterized by extensive mucus secretion and local cessation of acid secretion.

Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton.

T cell receptor (TCR)-driven activation of helper T cells induces a rapid polarization of their cytoskeleton towards bound antigen presenting cells (APCs). We have identified the Fyn- and SLP-76-associated protein Fyb/SLAP as a new ligand for Ena/ vasodilator-stimulated phosphoprotein (VASP) homology 1 (EVH1) domains. Upon TCR engagement, Fyb/SLAP localizes at the interface between T cells and anti-CD3-coated beads, where Evl, a member of the Ena/VASP family, Wiskott-Aldrich syndrome protein (WASP) and the Arp2/3 complex are also found. In addition, Fyb/SLAP is restricted to lamellipodia of spreading platelets. In activated T cells, Fyb/SLAP associates with Ena/VASP family proteins and is present within biochemical complexes containing WASP, Nck, and SLP-76. Inhibition of binding between Fyb/SLAP and Ena/VASP proteins or WASP and the Arp2/3 complex impairs TCR-dependent actin rearrangement, suggesting that these interactions play a key role in linking T cell signaling to remodeling of the actin cytoskeleton.