title: Local downregulation of enterochromaffin-like cell histamine formation in ulcer healing: a study in rats.
abstract: OBJECTIVE
  Although enterochromaffin-like (ECL) cells are the major source of histamine for the regulation of gastric acid secretion, their role in ulcer healing has not been fully investigated. The present study aimed to investigate changes in ECL cell components as well as markers for somatostatin cells, parietal cells and macrophages during the healing of experimental ulcers in rats.
  
  
  METHODS
  Standardised ulcer was induced directly in the rat gastric mucosa by brief application of acetic acid. At different time intervals following ulcer induction (1-15 days), histamine, histidine decarboxylase (HDC), chromogranin A, pancreastatin, vesicular monoamine transporter 2 (VMAT-2), H-K-ATPase, somatostatin as well as ED1 and ED2 (macrophage markers) were localised by immunocytochemistry. ED1- and histamine-immunoreactive cells were counted at different time points. HDC- and VMAT-2-immunoreactive cells were demonstrated by double staining and counted. The mRNA of HDC, chromogranin A and somatostatin was demonstrated by in situ hybridisation and quantitated by computerised image analysis.
  
  
  RESULTS
  HDC immunoreactivity and mRNA were markedly reduced in the ECL cells at the ulcer margin from day 1 following ulcer induction and onwards; after day 5 HDC immunoreactivity and mRNA rose gradually and had almost normalised by day 15. This local and transient downregulation of HDC was accompanied by a similar decrease in ECL cell histamine. In contrast to HDC and histamine, other ECL cell components (chromogranin A, pancreastatin, VMAT-2) as well as somatostatin and H-K ATPase were still demonstrable at the ulcer margin and displayed no major changes at any time point studied. Of the macrophage markers, ED1, but not ED2, could be identified at the ulcer margin, and the number of ED1-immunoreactive cells was high in the ulcer margin from day 1 to day 5 after ulcer induction. The increase in ED1-positive cells and the decrease in HDC-expressing cells were coincident in time and localisation.
  
  
  CONCLUSIONS
  The present results revealed a local and transient downregulation of HDC in the ECL cells at the ulcer margin. This may account for the decrease in ECL cell histamine observed. The local infiltration of macrophages into the ulcer margin suggests that inflammatory mediators are involved in the local suppression of ECL cell activity during ulcer healing.
authors.affiliation: Department of Physiology and Neuroscience, Lund University, Lund, Sweden.
authors.forename: Q
authors.initials: Q
authors.lastname: Mei
authors.forename: F
authors.initials: F
authors.lastname: Sundler
mesh_terms: D019342:Acetic Acid; D000818:Animals; D053379:Chromogranin A; D002864:Chromogranins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D019861:Enterochromaffin-like Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D006632:Histamine / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008264:Macrophages / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D053379:Chromogranin A; D002864:Chromogranins; D012333:RNA, Messenger; D013004:Somatostatin; D006632:Histamine; D006640:Histidine Decarboxylase; D019342:Acetic Acid