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Cooperation between IgG receptors (FcγRIIa) and TLR4 in human neutrophils
Author(s) -
Fudala Rafal,
Stankowska Dorota,
Krupa Agnieszka,
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.710.4
Subject(s) - ards , tlr4 , autoantibody , immunology , receptor , antibody , chemotaxis , sepsis , medicine , chemistry , inflammation , lung
Previous studies from our laboratory revealed that the presence of anti‐IL‐8 autoantibody:IL‐8 complexes in lung fluids from patients with ALI/ARDS is an important prognostic indicator for the development and outcome of ALI/ARDS. Further, we showed that purified anti‐IL‐8 autoantibody:IL‐8 complexes trigger chemotaxis of neutrophils, induce activation of these cells, and prolong the lifespan of neutrophils via IgG receptors, FcγRIIa. Sepsis is considered the major risk factor for development of ALI/ARDS, and LPS has been recognized as a causative factor for progression to ALI/ARDS. In the current study we demonstrated that the expression of FcγRIIa is increased in human neutrophils after LPS treatment. TLR4 and FcγRIIa co‐localize in LPS stimulated neutrophils but not in unstimulated cells. The interaction between TLR4 and FcγRIIa was confirmed by FRET (Fluorescence Resonance Energy Transfer). Treatment with LPS also enhances the pro‐inflammatory activity of anti‐IL‐8:IL‐8 complexes in neutrophils. We observed a substantial increase in the amount of myeloperoxidase in neutrophils pre‐treated with LPS and simulated with the complexes, elevated activation of NFκB and ERK. Our findings indicate that LPS affects activity of anti‐IL‐8:IL‐8 complexes by increasing expression of FcγRIIa, and evoking structural changes that lead to TLR4 and FcγRIIa clustering. Supported by the NIH grant HL073245.