Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes.
BACKGROUND: Recognition of lipopolysaccharide (LPS) is required for effective defense against invading gram-negative bacteria. Recently, in vitro studies revealed that CD14 is required for activation of the myeloid differentiation factor (MyD)88-dependent Toll-like receptor (TLR)4 signaling pathway...
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doaj-12882145d0924984941f71fe02c487182020-11-25T01:06:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0154e1018310.1371/journal.pone.0010183Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes.Adam A AnasJoppe W R HoviusCornelis van 't VeerTom van der PollAlex F de VosBACKGROUND: Recognition of lipopolysaccharide (LPS) is required for effective defense against invading gram-negative bacteria. Recently, in vitro studies revealed that CD14 is required for activation of the myeloid differentiation factor (MyD)88-dependent Toll-like receptor (TLR)4 signaling pathway by smooth (S)-LPS, but not by rough (R)-LPS. The present study investigated the role of CD14 in induction of lung inflammation in mice by these different LPS chemotypes. METHODOLOGY/RESULTS: Neutrophil accumulation and tumor necrosis factor (TNF) release in bronchoalveolar lavage fluid were determined 6 hours after intranasal treatment of wild type (WT) and CD14 knock-out (KO) mice with different doses S-LPS or R-LPS. The contribution of CD14 to lung inflammation induced by S-LPS or R-LPS depended on the LPS dose. At low doses, S-LPS and R-LPS induced neutrophil influx in a CD14-dependent manner. Low dose S-LPS-induced cytokine release also depended on CD14. Strikingly, neutrophil influx and TNF release induced by high dose S-LPS or R-LPS was diminished in the presence of CD14. Intranasal administration of sCD14 to CD14 KO mice treated with S-LPS partially reversed the inflammatory response to the response observed in WT mice. CONCLUSIONS: In conclusion, CD14 modulates effects of both S-LPS and R-LPS within the lung in a similar way. Except for R-LPS-induced TNF release, S-LPS and R-LPS at low dose induced acute lung inflammation in a CD14-dependent manner, while the inflammatory response triggered by high dose S-LPS or R-LPS was diminished by CD14.http://europepmc.org/articles/PMC2855719?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Adam A Anas Joppe W R Hovius Cornelis van 't Veer Tom van der Poll Alex F de Vos |
spellingShingle |
Adam A Anas Joppe W R Hovius Cornelis van 't Veer Tom van der Poll Alex F de Vos Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes. PLoS ONE |
author_facet |
Adam A Anas Joppe W R Hovius Cornelis van 't Veer Tom van der Poll Alex F de Vos |
author_sort |
Adam A Anas |
title |
Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes. |
title_short |
Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes. |
title_full |
Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes. |
title_fullStr |
Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes. |
title_full_unstemmed |
Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes. |
title_sort |
role of cd14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2010-01-01 |
description |
BACKGROUND: Recognition of lipopolysaccharide (LPS) is required for effective defense against invading gram-negative bacteria. Recently, in vitro studies revealed that CD14 is required for activation of the myeloid differentiation factor (MyD)88-dependent Toll-like receptor (TLR)4 signaling pathway by smooth (S)-LPS, but not by rough (R)-LPS. The present study investigated the role of CD14 in induction of lung inflammation in mice by these different LPS chemotypes. METHODOLOGY/RESULTS: Neutrophil accumulation and tumor necrosis factor (TNF) release in bronchoalveolar lavage fluid were determined 6 hours after intranasal treatment of wild type (WT) and CD14 knock-out (KO) mice with different doses S-LPS or R-LPS. The contribution of CD14 to lung inflammation induced by S-LPS or R-LPS depended on the LPS dose. At low doses, S-LPS and R-LPS induced neutrophil influx in a CD14-dependent manner. Low dose S-LPS-induced cytokine release also depended on CD14. Strikingly, neutrophil influx and TNF release induced by high dose S-LPS or R-LPS was diminished in the presence of CD14. Intranasal administration of sCD14 to CD14 KO mice treated with S-LPS partially reversed the inflammatory response to the response observed in WT mice. CONCLUSIONS: In conclusion, CD14 modulates effects of both S-LPS and R-LPS within the lung in a similar way. Except for R-LPS-induced TNF release, S-LPS and R-LPS at low dose induced acute lung inflammation in a CD14-dependent manner, while the inflammatory response triggered by high dose S-LPS or R-LPS was diminished by CD14. |
url |
http://europepmc.org/articles/PMC2855719?pdf=render |
work_keys_str_mv |
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