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Critical role of IgG receptors (FcγRs) in LPS‐induced severe lung inflammation
Author(s) -
Krupa Agnieszka,
Fudala Rafal,
Stankowska Dorota,
Kurdowska Anna
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.672.48
Subject(s) - syk , receptor , inflammation , tlr4 , autoantibody , ards , chemistry , immunology , lung , immune system , signal transduction , medicine , antibody , biochemistry , tyrosine kinase
Previously we showed that anti‐IL‐8:IL‐8 complexes (IL‐8 associated with anti‐IL‐8 autoantibodies) present in lungs of patients with ALI/ARDS correlate with both the development and outcome of ALI/ARDS. We also demonstrated that anti‐KC autoantibody:KC immune complexes (KC ‐ functional IL‐8) are present in the alveolar spaces of mice treated with LPS. Activity of these complexes is mediated by IgG receptors (FcγRs) because alveolar inflammatory response was substantially diminished in γ‐chain deficient (KO) mice that lack these receptors. In the current study we established that the expression of TLR4 and FcγRs is increased in lungs of mice treated with LPS, and that these receptors partially co‐localize. Further, Yes/Src was activated in neutrophils obtained from LPS treated mice at 6 and 14 h but not 2h, and was not detected in KO mice. Thus, activation of Yes at 6 and 14 h is a consequence of engagement of FcγRs by anti‐KC:KC complexes which are formed in lungs at around 6 h after LPS administration, and is unique for the FcγR signaling pathway. In contrast, we detected phosphorylated Syk already at 2 h since Syk is also activated through TLR4. Lack of activated Syk in KO mice at 6 and 14h indicates that activation of Syk is induced via FcγRs, by the anti‐KC:KC complexes that appear in the lungs at 6 h. Our results suggest a possible crosstalk between TLR4 and FcγRs in lung inflammation. Supported by the NIH grant HL073245.