title: The LPS receptor generates inflammatory signals from the cell surface.
abstract: Bacterial lipopolysaccharides (LPSs) are recognized in mammals by a receptor complex composed of CD14, Toll-like receptor 4 (TLR4), and MD-2. The mechanism of TLR4 function remains to be elucidated. We constructed chimeric TLR molecules C-terminally fused to fluorescent proteins and stably expressed these chimeric constructs in cells. Confocal microscopy revealed TLR4 to be expressed on the plasma membrane and the Golgi apparatus. Time-lapse confocal imaging showed rapid recycling of TLR4/CD14/MD-2 complexes between the Golgi and the plasma membrane. Membrane TLR4 engagement by antibody was sufficient to induce signaling and pharmacological disruption of the Golgi did not affect cellular responses to LPS. Thus, LPS signaling commences after LPS recognition by surface-expressed TLR4 independent of LPS trafficking to the Golgi.
authors.affiliation: Division of Infectious Diseases, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA. eicke.latz@umassmed.edu
authors.forename: Eicke
authors.initials: E
authors.lastname: Latz
authors.forename: Alberto
authors.initials: A
authors.lastname: Visintin
authors.forename: Egil
authors.initials: E
authors.lastname: Lien
authors.forename: Kate A
authors.initials: KA
authors.lastname: Fitzgerald
authors.forename: Terje
authors.initials: T
authors.lastname: Espevik
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003470:Culture Media; D004797:Enzyme-Linked Immunosorbent Assay; D006056:Golgi Apparatus / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008164:Luminescent Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D003470:Culture Media; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins