Role of intercellular adhesion molecule-1 in a murine model of toluene diisocyanate-induced asthma.
BACKGROUND
Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) are thought to contribute to the airway inflammation and airway hyper-responsiveness (AHR) of allergic asthma. Some differences from allergic asthma have been noted, including airway neutrophilia, and the involvement of ICAM-1 in toluene diisocyanate (TDI) asthma is currently unclear.


OBJECTIVE
We utilized mice lacking ICAM-1 expression (ICAM-1(-/-)) to investigate the role of ICAM-1 in airway inflammation and AHR in TDI-induced asthma.


METHODS
Male C57BL/6J mice (ICAM-1(+/+)) and ICAM-1(-/-) mice were intranasally sensitized to TDI solution or solvent alone. Airway inflammation, AHR and cytokine secretion were assessed 24 h after challenge by TDI or solvent. The production of antigen-specific IgG and IgE by TDI sensitized and non-sensitized mice was determined.


RESULTS
TDI challenge to ICAM-1(+/+) mice induced an increase in airway inflammatory cell numbers, AHR and cytokine secretion of TNF-alpha, macrophage inflammatory protein-2 (MIP-2), IL-4, IL-5 and IFN-gamma into the bronchoalveolar lavage fluid. All these pathophysiological changes were reduced in ICAM-1(-/-) mice. Serum levels of TDI-specific IgG and IgE of ICAM-1(-/-) and ICAM-1(+/+) mice were comparable.


CONCLUSIONS
These results suggest that ICAM-1 plays an essential role in airway inflammation and AHR in TDI-induced asthma.
Furusho
S
S
Departments of Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Ishikawa, Japan. sfurusho@med3.m.kanazawa-u.ac.jp
Myou
S
S
Fujimura
M
M
Kita
T
T
Yasui
M
M
Kasahara
K
K
Nakao
S
S
Takehara
K
K
Sato
S
S
D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016085:Bronchoconstrictor Agents; D054426:Chemokine CXCL2; D018925:Chemokines / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009784:Occupational Diseases / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D016085:Bronchoconstrictor Agents; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D007074:Immunoglobulin G; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D016210:Methacholine Chloride; D018799:Intercellular Adhesion Molecule-1; D014051:Toluene 2,4-Diisocyanate; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma