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Mechanisms of impaired eosinophil recruitment and humoral response induced by endotoxin tolerance in murine asthma
Author(s) -
Natarajan Sudha,
Kim Jiyoun,
Remick Daniel G.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.166.12
Subject(s) - eotaxin , immunology , eosinophil , inflammation , immunoglobulin e , medicine , bronchial hyperresponsiveness , chemokine , asthma , methacholine , allergic inflammation , antibody , lung , respiratory disease
Previous data suggest that persistent endotoxin (ENDO) exposure protects against inflammation induced by allergen challenge. We hypothesized that persistent exposure to ENDO results in ENDO tolerance (ET) and a specific reduction in both cellular and humoral immunity. ET was induced in female BALB/c mice by direct intratracheal installation of 1ug of ENDO for 4 consecutive days. On day 5, mice were immunized with 2ug cockroach allergen, challenged on days 14 & 21 and sacrificed at subsequent timepoints. Airways hyperresponsiveness to methacholine was significantly increased in ET (350% above baseline) vs. non ET (144%) mice. Numbers of eosinophils recruited to the lung (ET vs. non‐ET, 14,486vs.74,636), eosinophil specific peroxidase activity and pulmonary levels of eotaxin (67pg/ml vs. 48) and eotaxin‐2 (2349 vs. 249) were significantly decreased in ET mice. Differences were not seen in other eosinophil chemoattractants IL‐5 or RANTES. Neutrophil numbers, CXC chemokines, and pulmonary expression of Th1 (IFN‐g;, IL‐12) and Th2 (IL‐4, 5, 13) cytokines were not affected by ET, although plasma IgE (141ng vs. 45) and IgM (11ug vs. 7) were significantly decreased in ET mice. Our data indicate ET specifically blunts eosinophilic inflammation and the humoral response to allergen challenge, providing mechanistic insight into protection from asthmatic inflammation.