HCl-induced inflammatory mediators in esophageal mucosa increase migration and production of H2O2 by peripheral blood leukocytes.
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.
Ma
Jie
J
Department of Medicine, Rhode Island Hospital, Brown University, Providence, USA.
Altomare
Annamaria
A
de la Monte
Suzanne
S
Tong
Ming
M
Rieder
Florian
F
Fiocchi
Claudio
C
Behar
Jose
J
Shindou
Hideo
H
Biancani
Piero
P
Harnett
Karen M
KM
D000818:Animals; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006851:Hydrochloric Acid / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D009092:Mucous Membrane / Q000378:metabolism*; D011817:Rabbits
D007375:Interleukin-1; D006861:Hydrogen Peroxide; D006851:Hydrochloric Acid