Document Detail


HCl-induced inflammatory mediators in esophageal mucosa increase migration and production of H2O2 by peripheral blood leukocytes.
MedLine Citation:
PMID:  20616304     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 H(2)O(2) as 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 degrees 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 H(2)O(2) production. 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 H(2)O(2) release 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 H(2)O(2) by PBL. These findings provide a direct link between acid exposure and recruitment and activation of immune cells in esophageal mucosa.
Authors:
Jie Ma; Annamaria Altomare; Suzanne de la Monte; Ming Tong; Florian Rieder; Claudio Fiocchi; Jose Behar; Hideo Shindou; Piero Biancani; Karen M Harnett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-08
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  299     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-30     Completed Date:  2010-09-24     Revised Date:  2011-09-13    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G791-8     Citation Subset:  IM    
Affiliation:
Department of Medicine, Rhode Island Hospital, Brown University, Providence, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Esophagus / drug effects*,  physiology
Gene Expression Regulation / physiology
Hydrochloric Acid / toxicity*
Hydrogen Peroxide / metabolism*
Inflammation / chemically induced*,  metabolism
Interleukin-1 / genetics,  metabolism
Leukocytes / metabolism*
Mucous Membrane / metabolism*
Rabbits
Grant Support
ID/Acronym/Agency:
R01 DK57030/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-1; 7647-01-0/Hydrochloric Acid; 7722-84-1/Hydrogen Peroxide
Comments/Corrections

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