In the lung, binding of LPS to TLR4 is infl uenced by a number of surfactant proteins (SP), including SP-A, SP-C and SP-D [15] . Th ese surfactants are able to infl uence the interaction between TLR4 and LPS by direct binding to LPS; i.e., SP-A binds to rough LPS and lipid A, but not to smooth LPS, SP-C also binds to rough LPS, and SP-D binds to both rough and smooth LPS. SP-A and SP-C binding to LPS inhibits TNF secretion by alveolar macrophages, whereas SP-D binding to LPS moderately enhances TNF secretion by alveolar macrophages. In addition, SP-A, SP-C and SP-D also bind to CD14 at the site which recognizes LPS. Strikingly, binding of SP-A to CD14 enhanced the binding of rough LPS and binding of SP-C to CD14 augmented binding of smooth LPS [15] , whereas binding of SP-A to CD14 reduced binding of smooth LPS and binding of SP-D to CD14 decreased binding of both smooth and rough LPS. Furthermore, SP-D infl uences LPS-induced TNF secretion by alveolar macrophages by regulating matrix metalloproteinasemediated cleavage of CD14 from the surface of these cells [16] .