ICAM-1-dependent pathways regulate colonic eosinophilic inflammation.
Eosinophilic inflammation is a common feature of numerous eosinophil-associated gastrointestinal (EGID) diseases. Central to eosinophil migration into the gastrointestinal tract are the integrin-mediated interactions with adhesion molecules. Although the mechanisms regulating eosinophil homing into the small intestine have begun to be elucidated, the adhesion pathways responsible for eosinophil trafficking into the large intestine are unknown. We investigated the role of adhesion pathways in eosinophil recruitment into the large intestine during homeostasis and disease. First, using a hapten-induced colonic injury model, we demonstrate that in contrast to the small intestine, eosinophil recruitment into the colon is regulated by a beta7 -integrin addressin cell adhesion molecule-1-independent pathway. Characterization of integrin expression on colonic eosinophils by flow cytometry analysis revealed that colonic CC chemokine receptor 3+ eosinophils express the intercellular adhesion molecule-1 (ICAM-1) counter-receptor integrins alphaL, alphaM, and beta2. Using ICAM-1-deficient mice and anti-ICAM-1 neutralizing antibodies, we show that hapten-induced colonic eosinophilic inflammation is critically dependent on ICAM-1. These studies demonstrate that beta2 -integrin/ICAM-1-dependent pathways are integral to eosinophil recruitment into the colon during GI inflammation associated with colonic injury.
Forbes
Elizabeth
E
Allergy and Inflammation Research Group, Division of Biochemistry and Molecular Biology, The John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Hulett
Mark
M
Ahrens
Richard
R
Wagner
Norbert
N
Smart
Vanessa
V
Matthaei
Klaus I
KI
Brandt
Eric B
EB
Dent
Lindsay A
LA
Rothenberg
Marc E
ME
Tang
Mimi
M
Foster
Paul S
PS
Hogan
Simon P
SP
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D002465:Cell Movement; D003092:Colitis / Q000276:immunology*; D003106:Colon / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D039001:Integrin alpha Chains / Q000502:physiology; D039641:Integrin beta Chains / Q000378:metabolism / Q000502:physiology / Q000506:poisoning; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism
D018821:CD18 Antigens; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; C091368:integrin beta7; D018799:Intercellular Adhesion Molecule-1