In contrast to rabbits, administration of LPS alone to lungs of naive mice induced severe pneumonitis, irrespective of the manner of LPS delivery (inhalation or intra tracheal or intranasal instillation) or the source of LPS (Escherichia coli or Acinetobacter baumannii). Using antibody-treated and gene-defi cient mice, CD14 was found to be critically involved in the development of LPS-induced lung infl ammation [23] [24] [25] [26] . A study with CD14-defi cient mice and TLR4 mutant mice (lacking a functional TLR4) showed that LPS-induced vascular leakage, neutrophil infi ltration, nuclear translocation of NF-κB. Th e release of cytokines (TNF and IL-6) and chemo kines (CXCL1 and CXCL2) in the lung was completely dependent on these pattern recognition receptors [24] . Similar observations were made by others using mice treated intravenously with anti-CD14 Infl uenza A mouse CD14 -/-/~clearance, ~lymphocyte recruitment and activation, ~neutrophil infl ux, 50 ~cytokines antibodies [23] and by our group using CD14-defi cient and TLR4-defi cient mice [25] . Furthermore, intratracheal treatment of CD14-defi cient mice with sCD14 restored the infl ammatory response to the level present in wildtype mice, whereas treatment with wild-type alveolar macrophages restored the neutrophil infi ltration of the lung but not pulmonary TNF release [26] . Moreover, treatment with wild-type alveolar macrophages also restored neutrophil infi ltration in the lung of LPSexposed TLR4-defi cient mice [27] . Th ese fi ndings indicate that sCD14, and CD14 and TLR4 on the surface of alveolar macrophages contribute to the development of LPS-induced lung infl ammation. However, when a high dose of LPS was administered to the lungs of mice, acute lung infl ammation was absent in mice lacking functional TLR4, but only partially reduced in CD14 defi cient mice [24] . Th us, LPS-induced lung infl am mation is entirely dependent on TLR4 and, depending on the dose of LPS, also on the presence of CD14 in the lung.