Premium
TLR4 enhances resolution of lung inflammation by promoting neutrophil apoptosis
Author(s) -
zhao hang,
Dedaj rejmon,
zhao gao feng,
leu shaw wei,
shen lian jun,
lien egil,
fitzgerald Kate,
Shiedlin Aviva,
quinn deborah ann,
hales charles a
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.672.53
Subject(s) - ards , bronchoalveolar lavage , inflammation , tlr4 , medicine , chemokine , lung , immunology , diffuse alveolar damage , apoptosis , pulmonary edema , alveolar macrophage , macrophage , acute respiratory distress , biology , in vitro , biochemistry
Acute lung injury (ALI), the called acute respiratory distress syndrome in its most severe (ARDS) clinical manifestation, affects about 150,000 patients per year in the US, with recent mortality rates being > 30%. High concentrations of hyaluronan (HA) are found in bronchoalveolar lavage (BAL) fluid of ARDS patients. Neutrophils appear to play a major role in the development of ALI/ARDS. Here we report that in response to inhaled low molecular weight HA (LMW HA), mice lacking the TLR4‐MyD88 independent signaling pathway showed loss of lung epithelial integrity, diffuse alveolar damage, increased interstitial edema, increased inflammatory cytokines and chemokines, including macrophage inflammatory protein (MIP‐2) (a rodent homolog of IL‐8), interleukin (IL)‐6 and KC compared to wild type. In addition, there were large numbers of activated neutrophils in BAL fluid and lung interstitium in TLR4 knock out mice, indicating TLR4 enhances the resolution of inflammation by promoting apoptosis of neutrophils. Our findings show an unrecognized potential for the treatment of ALI/ARDS disorders. This work was supported by a training grant from the NIH (HL007874 to H.Z.)