DOI: 10.1084/jem.185.12.2095. Mice Genetically Hyporesponsive to Lipopolysaccharide (LPS) Exhibit a Defect in Endocytic Uptake of LPS and Ceramide

Mice Genetically Hyporesponsive to Lipopolysaccharide (LPS) Exhibit a Defect in Endocytic Uptake of LPS and Ceramide

10.1084/jem.185.12.2095

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

We have recently shown that monomeric bacterial LPS is rapidly delivered from the plasma membrane to an intracellular site and that agents that block vesicular transport block responses of neutrophils to lipopolysaccharide (LPS) (Detmers, P.A., N. Thiéblemont, T. Vasselon, R. Pironkova, D.S. Miller, and S.D. Wright. 1996. J. Immunol. 157:5589–5596). To examine further the connection between intracellular transport of LPS and signaling, we observed internalization of fluorescently labeled LPS in cells from LPS-hyporesponsive (Lpsd) mice. Binding of fluorescent LPS from LPS–soluble CD14 (sCD14) complexes by peritoneal macrophages from Lpsd and control (Lpsn) mice was quantitatively similar, and confocal images obtained from these cells exhibited an identical appearance immediately after labeling. Incubation of labeled Lpsn macrophages at 37°C caused movement of the fluorescence from the cell perimeter in one or two spots in the perinuclear region. However, in Lpsd cells the fluorescence remained dispersed, suggesting a defect in vesicular transport. LPS resembles ceramide, and Lpsd mice fail to respond to ceramide. As with LPS, we found that binding of fluorescent ceramide by Lpsd and Lpsn macrophages was quantitatively similar, and the label moved rapidly to one to two spots in the perinuclear region in Lpsn mice. However, in Lpsd macrophages the fluorescence remained dispersed. These results show that cells deficient in responses to LPS exhibit defective vesicular transport of LPS and ceramide and point to a role for vesicular transport in responses to these mediators.

Bibliography

ThiÃ©blemont, N., & Wright, S. D. (1997). Mice Genetically Hyporesponsive to Lipopolysaccharide (LPS) Exhibit a Defect in Endocytic Uptake of LPS and Ceramide. The Journal of Experimental Medicine, 185(12), 2095â2100.

Authors 2

Nathalie Thiéblemont (first)
Samuel D. Wright (additional)

References 30 Referenced 48

10.1084/jem.179.1.269 / J Exp Med / Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14 by Hailman (1994)
10.1084/jem.181.5.1743 / J Exp Med / Soluble CD14 acts as a shuttle in the neutralization of lipopolysaccharide (LPS) by LPS-binding protein and reconstituted high density lipoprotein by Wurfel (1995)
10.4049/jimmunol.156.11.4384 / J Immunol / Stimulation of macrophages and neutrophils by complexes of lipopolysaccharide and soluble CD14 by Hailman (1996)
10.4049/jimmunol.157.12.5589 / J Immunol / Potential role of membrane internalization and vesicle fusion in adhesion of neutrophils in response to lipopolysaccharide and TNF by Detmers (1996)
10.1038/2191253a0 / Nature (Lond) / Genetic control of the leukocyte responses to endotoxin by Sultzer (1968)
10.4049/jimmunol.122.2.619 / J Immunol / Characterization of a congenitally LPS-resistant, athymic mouse strain by Vogel (1979)
10.1007/BF01843983 / Immunogenetics / Genetic basis for unresponsiveness to lipopolysaccharide in C57BL/10Cr mice by Coutinho (1978)
{'key': '2023072507024632300_B8', 'first-page': '67', 'article-title': 'Non-specific responses of C3H/He low responder mice to LPS and to TCAextracted endotoxin', 'volume': '128', 'author': 'Damais', 'year': '1977', 'journal-title': 'Ann Immunol (Paris)'} / Ann Immunol (Paris) / Non-specific responses of C3H/He low responder mice to LPS and to TCAextracted endotoxin by Damais (1977)
10.4049/jimmunol.133.1.299 / J Immunol / LPS regulation of the immune response: bacteroidesendotoxin induces mitogenic, polyclonal, and antibody responses in classical LPS responsive but not C3H/HeJ mice by Wannemuehler (1984)
{'key': '2023072507024632300_B10'}
10.1074/jbc.271.8.4100 / J Biol Chem / Catalytic properties of lipopolysaccharide (LPS) binding protein. Transfer of LPS to soluble CD14 by Yu (1996)
10.1021/bi00412a034 / Biochemistry / A series of fluorescent N-acetylsphingosines: synthesis, physical properties, and studies in cultured cells by Pagano (1988)
10.4049/jimmunol.155.4.2085 / J Immunol / Endotoxin receptors (CD14) are found with CD16 (Fc gamma RIII) in an intracellular compartment of neutrophils that contains alkaline phosphatase by Detmers (1995)
10.4049/jimmunol.120.2.422 / J Immunol / The genetic mapping of a defective LPS response gene in C3H/ HeJ mice by Watson (1978)
{'key': '2023072507024632300_B15'}
10.1016/0092-8674(94)90147-3 / Cell / The sphingomyelin pathway in tumor necrosis factor and interleukin-1 signaling by Kolesnick (1994)
10.4049/jimmunol.155.5.2303 / J Immunol / Defective ceramide response in C3H/HeJ (Lpsd)macrophages by Barber (1995)
10.1016/S0021-9258(17)32484-5 / J Biol Chem / Bacterial lipopolysaccharide has structural similarity to ceramide and stimulates ceramide-activated protein kinase in myeloid cells by Joseph (1994)
10.1083/jcb.113.6.1267 / J Cell Biol / A novel fluorescent ceramide analogue for studying membrane traffic in animal cells: accumulation at the Golgi apparatus results in altered spectral properties of the sphingolipid precursor by Pagano (1991)
10.1126/science.2581316 / Science (Wash DC) / A vital stain for the Golgi apparatus by Lipsky (1985)
10.1016/S0021-9258(17)41834-5 / J Biol Chem / The sphingomyelin cycle and the second messenger function of ceramide by Hannun (1994)
10.1083/jcb.111.3.977 / J Cell Biol / Generation of lipid polarity in intestinal epithelial (Caco-2) cells: sphingolipid synthesis in the Golgi complex and sorting before vesicular traffic to the plasma membrane by van't Hof (1990)
10.1016/0167-5699(95)80185-5 / Immunol Today / Does endotoxin stimulate cells by mimicking ceramide? by Wright (1995)
10.4049/jimmunol.137.12.3921 / J Immunol / Ganglioside expression in macrophages from endotoxin responder and nonresponder mice by Yohe (1986)
10.4049/jimmunol.146.6.1900 / J Immunol / The presence of sialidase-sensitive sialosylgangliotetrasoyl ceramide (GM1b) in stimulated murine macrophages. Deficiency of GM1b in Escherichia coli– activated macrophages from the C3H/HeJ mouse by Yohe (1991)
10.1128/iai.52.3.777-785.1986 / Infect Immun / Membrane glycolipid and phospholipid composition of lipopolysaccharide-responsive and -nonresponsive murine B lymphocytes by Chaby (1986)
10.4049/jimmunol.151.2.959 / J Immunol / Binding, internalization, and deacylation of bacterial lipopolysaccharide by human neutrophils by Luchi (1993)
10.1128/iai.48.2.464-473.1985 / Infect Immun / Uptake and deacylation of bacterial lipopolysaccharides by macrophages from normal and endotoxin-hyporesponsive mice by Munford (1985)
10.1126/science.274.5290.1194 / Science (Wash DC) / Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors by Rosette (1996)
10.1126/science.274.5295.2086 / Science (Wash DC) / Control of EGF receptor signaling by clathrin-mediated endocytosis by Vieira (1996)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:48 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 3:34 a.m.)
Indexed	5 months ago (March 31, 2025, 12:07 p.m.)
Issued	28 years, 2 months ago (June 16, 1997)
Published	28 years, 2 months ago (June 16, 1997)
Published Online	28 years, 2 months ago (June 16, 1997)
Published Print	28 years, 2 months ago (June 16, 1997)

Funders 0

None

BibTeX

@article{Thi_blemont_1997, title={Mice Genetically Hyporesponsive to Lipopolysaccharide (LPS) Exhibit a Defect in Endocytic Uptake of LPS and Ceramide}, volume={185}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.185.12.2095}, DOI={10.1084/jem.185.12.2095}, number={12}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Thiéblemont, Nathalie and Wright, Samuel D.}, year={1997}, month=jun, pages={2095–2100} }

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  "URL": "http://dx.doi.org/10.1084/jem.185.12.2095",
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  "ISSN": [
    "0022-1007",
    "1540-9538"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        1997,
        6,
        16
      ]
    ]
  }
}