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HCl-induced inflammatory mediators in esophageal mucosa increase migration and production of H2O2by peripheral blood leukocytes
- Source :
- American Journal of Physiology-Gastrointestinal and Liver Physiology. 299:G791-G798
- Publication Year :
- 2010
- Publisher :
- American Physiological Society, 2010.
-
Abstract
- Exposure of esophageal mucosa to hydrochloric acid (HCl) is a crucial factor in the pathogenesis of reflux disease. We examined supernatant of HCl-exposed rabbit mucosa for inflammatory mediators enhancing migration of leukocytes and production of H2O2as an indicator of leukocyte activation. A tubular segment of rabbit esophageal mucosa was tied at both ends to form a sac, which was filled with HCl-acidified Krebs buffer at pH 5 (or plain Krebs buffer as control) and kept oxygenated at 37°C. The medium around the sac (supernatant) was collected after 3 h. Rabbit peripheral blood leukocytes (PBL) were isolated, and sac supernatant was used to investigate PBL migration and H2O2production. HCl-exposed esophageal mucosa released substance P (SP), CGRP, platelet-activating factor (PAF), and IL-8 into the supernatant. PBL migration increased in response to IL-8 or to supernatant of the HCl-filled mucosal sac. Supernatant-induced PBL migration was inhibited by IL-8 antibodies and by antagonists for PAF (CV3988) or neurokinin 1 (i.e., SP), but not by a CGRP antagonist. Supernatant of the HCl-filled mucosal sac increased H2O2release by PBL that was significantly reduced by CV3988 and by a SP antagonist but was not affected by IL-8 antibodies or by a CGRP antagonist. We conclude that IL-8, PAF, and SP are important inflammatory mediators released by esophageal mucosa in response to acid that promote PBL migration. In addition, PAF and SP induce production of H2O2by PBL. These findings provide a direct link between acid exposure and recruitment and activation of immune cells in esophageal mucosa.
- Subjects :
- Pathology
medicine.medical_specialty
Physiology
medicine.medical_treatment
Inflammation
Biology
Inflammation/Immunity/Mediators
Pathogenesis
Esophagus
Physiology (medical)
Leukocytes
medicine
Animals
Interleukin 8
Mucous Membrane
Hepatology
Esophageal disease
Gastroenterology
Mucous membrane
Interleukin
Hydrogen Peroxide
medicine.disease
Cytokine
medicine.anatomical_structure
Gene Expression Regulation
Hydrochloric Acid
Rabbits
medicine.symptom
Interleukin-1
Subjects
Details
- ISSN :
- 15221547 and 01931857
- Volume :
- 299
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Accession number :
- edsair.doi.dedup.....bf41169f257064634e56118f49c7b4ff