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Endotoxin tolerance induces selective alterations in neutrophil function
Author(s) -
Parker Lisa C.,
Jones Elizabeth C.,
Prince Lynne R.,
Dower Steven K.,
Whyte Moira K. B.,
Sabroe Ian
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0405236
Subject(s) - tlr4 , biology , phagocyte , immunology , lipopolysaccharide , chemokine , proinflammatory cytokine , toll like receptor , granulocyte , microbiology and biotechnology , signal transduction , receptor , inflammation , innate immune system , phagocytosis , immune system , biochemistry
Endotoxin tolerance has the potential to limit phagocyte responses to Toll‐like receptor (TLR) agonists, but the role of tolerance in regulating neutrophil responses is unknown. We investigated neutrophil responses to prolonged lipopolysaccharide (LPS) exposure and observed induction of tolerance in intracellular signaling pathways and respiratory burst. These effects were not prevented by granulocyte macrophage‐colony stimulating factor (GM‐CSF) pretreatment, and tolerized neutrophils retained the ability to respond to GM‐CSF and other survival factors with a delay in apoptosis. In addition, LPS‐exposed neutrophils showed continued generation of CXC chemokine ligand 8, which was not reduced in tolerized cells. Induction of tolerance was associated with a loss of TLR4 surface expression. Tolerance, therefore, induces a selective reprogramming of neutrophil function, but cells retain a predominantly proinflammatory phenotype.