Premium
An essential role for endothelial TLR4 in leukocyte recruitment
Author(s) -
Kubes Paul,
Andonegui Graciela,
Zhou Hong
Publication year - 2007
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.21.6.a849-c
Subject(s) - tlr4 , endothelium , immunology , biology , innate immune system , population , transgene , genetically modified mouse , immune system , microbiology and biotechnology , medicine , endocrinology , gene , biochemistry , environmental health
Recent work from our laboratory suggested that neutrophil recruitment into the lungs in response to systemic lipopolysaccaride was not due to TLR4 on leukocytes but rather on radiation‐resistant cells (eg. mast cells, endothelium, epithelium or fibroblasts). In this study we made a transgenic mouse that has TLR4 exclusively on endothelium (endo TLR4). These mice had no TLR4 on any leukocyte population but did have LPS responsive endothelium. LPS increased neutrophil recruitment into lungs in wild‐type but not in TLR4 deficient mice. Transgenic (endo TLR4) mice responded almost identically to wild‐type mice in terms of neutrophil recruitment into lungs. Examination of local LPS responses in muscle also revealed that wild‐type and transgenic endo TLR4 mice recruited ample neutrophils whereas TLR4 deficient mice had no responses. Our data suggest a very robust and effective neutrophil recruitment response when endothelium were the only cells expressing TLR4. The data further support the importance of endothelial TLR4 in innate immune responses.