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 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.


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.
Anas
Adam A
AA
Center for Infection and Immunity Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
Hovius
Joppe W R
JW
van 't Veer
Cornelis
C
van der Poll
Tom
T
de Vos
Alex F
AF
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002633:Chemotaxis; D004195:Disease Models, Animal; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils; D011014:Pneumonia / Q000139:chemically induced / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha