DOI: 10.1177/096805199400100104. Inhibition of LPS binding on human monocytes by phosphonooxyethyl analogs of lipid A

Inhibition of LPS binding on human monocytes by phosphonooxyethyl analogs of lipid A

10.1177/096805199400100104

Crossref journal-article

SAGE Publications

Journal of Endotoxin Research (179)

Abstract

We investigated the inhibition of LPS binding on human monocytes by synthetic analogs of lipid A. A common characteristic of the analyzed structures is a α-(or β-) phosphonooxyethyl group in position 1 of the GlcN I of the lipid A backbone. Compounds PE-1, PE-2 and PE-3 are analogs of synthetic Escherichia coli lipid A whereas PE-4 represents an analog of tetraacyl precursor Ia (synthetic compound 406). By determining the ability of these preparations to inhibit the binding of FITC-labeled LPS (E. coli 0111:B4) on human monocytes the relationship between their structure and cellular binding affinity was evaluated. The results showed a structure-dependent hierarchy of inhibition capacity. Thus, compound PE-1 inhibited the binding of FITC-LPS only slightly more than PE-2. However, compound PE-3, possessing β-configurated GlcN I, exhibited a drastically decreased inhibition capability. Best inhibition was obtained with compound PE-4. It was furthermore shown by a Lineweaver-Burk plot that the inhibition of LPS binding was due to competition of FITC-LPS and PE-4 for the same binding structure. The synthesis of stable 1-phosphonooxyethyl analogs of precursor Ia with high affinity for LPS receptor structures but lacking cytokine-inducing capacity (like PE-4) may be of relevance for their function as potent antagonists of LPS in therapy of endotoxic shock and sepsis.

Bibliography

Heine, H., Brade, H., Kusumoto, S., Kusama, T., Rietschel, E. Th., Flad, H.-D., & Ulmer, A. J. (1994). Inhibition of LPS binding on human monocytes by phosphonooxyethyl analogs of lipid A. Journal of Endotoxin Research, 1(1), 14â20.

Authors 7

H. Heine (first)
H. Brade (additional)
S. Kusumoto (additional)
T. Kusama (additional)
E. Th. Rietschel (additional)
H.-D. Flad (additional)
A.J. Ulmer (additional)

References 37 Referenced 20

10.1007/978-3-642-76412-7_16
10.1038/scientificamerican0892-54
10.1016/S0171-2985(89)80036-1
{'key': 'atypb4', 'first-page': '73', 'volume': '89', 'author': 'Feist W.', 'year': '1992', 'journal-title': 'Microbiol Immunol'} / Microbiol Immunol by Feist W. (1992)
10.1016/S0021-9258(18)55023-7
10.1038/352342a0
10.1002/eji.1830161013
10.1128/IAI.57.4.1336-1338.1989
{'key': 'atypb9', 'first-page': '23', 'volume': '11', 'author': 'Wang M-H.', 'year': '1992', 'journal-title': 'Lymphokine Cytokine Res'} / Lymphokine Cytokine Res by Wang M-H. (1992)
{'journal-title': 'FASEB J', 'year': '1993', 'author': 'Rietschel E Th', 'key': 'atypb10'} / FASEB J by Rietschel E Th (1993)
10.1128/IAI.61.6.2325-2333.1993
10.1084/jem.172.1.77
10.4049/jimmunol.142.9.3229 / J Immunol by Loppnow H. (1989)
10.1016/S0171-2985(11)80346-3
10.1128/IAI.58.11.3743-3750.1990
Loppnow H., Rietschel E Th, Brade H. et al. Lipid A precursor Ia (compound 406) and Rhodobacter capsulatus lipopolysaccharide: potent endotoxin antagonists in the human system in vitro . In: Levin J, Alving CR, Munford RS, Stütz PL, eds. Bacterial endotoxin: recognition and effector mechanisms. Amsterdam: Elsevier 1993: 337-348.
10.1128/IAI.60.12.5145-5152.1992
10.1016/S0171-2985(11)80338-4
10.1084/jem.176.2.485
10.1248/cpb.38.3366
10.1248/cpb.39.1994
10.1128/IAI.60.8.3309-3314.1992
{'key': 'atypb23', 'first-page': '226', 'volume': '243', 'author': 'Galanos C.', 'year': '1979', 'journal-title': 'Zentralbl Bakt Hyg A'} / Zentralbl Bakt Hyg A by Galanos C. (1979)
10.1246/bcsj.60.2205
10.1016/S0171-2985(84)80042-X
{'key': 'atypb26', 'first-page': '165', 'volume': '4', 'author': 'Earle W.R.', 'year': '1943', 'journal-title': 'J Natl Cancer Inst'} / J Natl Cancer Inst by Earle W.R. (1943)
10.4049/jimmunol.148.11.3505 / J Immunol by Heumann D. (1992)
10.1016/S0171-2985(11)80340-2
10.1096/fasebj.5.12.1916089
10.1016/0165-2478(93)90096-K
10.1016/0952-7915(91)90082-C
10.1016/0167-5699(93)90212-4
10.4049/jimmunol.141.2.547 / J Immunol by Haziot A. (1988)
10.1126/science.1698311
10.1126/science.2402637
10.1084/jem.170.4.1231
10.1016/S0065-2776(08)60502-7

Dates

Type	When
Created	17 years, 7 months ago (Jan. 25, 2008, 2:57 p.m.)
Deposited	6 months ago (March 1, 2025, 1:04 p.m.)
Indexed	6 months ago (March 2, 2025, 12:52 a.m.)
Issued	31 years, 6 months ago (March 1, 1994)
Published	31 years, 6 months ago (March 1, 1994)
Published Online	31 years, 6 months ago (March 1, 1994)
Published Print	31 years, 6 months ago (March 1, 1994)

Funders 0

None

BibTeX

@article{Heine_1994, title={Inhibition of LPS binding on human monocytes by phosphonooxyethyl analogs of lipid A}, volume={1}, ISSN={0968-0519}, url={http://dx.doi.org/10.1177/096805199400100104}, DOI={10.1177/096805199400100104}, number={1}, journal={Journal of Endotoxin Research}, publisher={SAGE Publications}, author={Heine, H. and Brade, H. and Kusumoto, S. and Kusama, T. and Rietschel, E. Th. and Flad, H.-D. and Ulmer, A.J.}, year={1994}, month=mar, pages={14–20} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        3,
        2
      ]
    ],
    "date-time": "2025-03-02T05:52:24Z",
    "timestamp": 1740894744420,
    "version": "3.38.0"
  },
  "reference-count": 37,
  "publisher": "SAGE Publications",
  "issue": "1",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            1994,
            3,
            1
          ]
        ],
        "date-time": "1994-03-01T00:00:00Z",
        "timestamp": 762480000000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://journals.sagepub.com/page/policies/text-and-data-mining-license"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1994,
        3
      ]
    ]
  },
  "abstract": "<jats:p> We investigated the inhibition of LPS binding on human monocytes by synthetic analogs of lipid A. A common characteristic of the analyzed structures is a \u03b1-(or \u03b2-) phosphonooxyethyl group in position 1 of the GlcN I of the lipid A backbone. Compounds PE-1, PE-2 and PE-3 are analogs of synthetic Escherichia coli lipid A whereas PE-4 represents an analog of tetraacyl precursor Ia (synthetic compound 406). By determining the ability of these preparations to inhibit the binding of FITC-labeled LPS (E. coli 0111:B4) on human monocytes the relationship between their structure and cellular binding affinity was evaluated. The results showed a structure-dependent hierarchy of inhibition capacity. Thus, compound PE-1 inhibited the binding of FITC-LPS only slightly more than PE-2. However, compound PE-3, possessing \u03b2-configurated GlcN I, exhibited a drastically decreased inhibition capability. Best inhibition was obtained with compound PE-4. It was furthermore shown by a Lineweaver-Burk plot that the inhibition of LPS binding was due to competition of FITC-LPS and PE-4 for the same binding structure. The synthesis of stable 1-phosphonooxyethyl analogs of precursor Ia with high affinity for LPS receptor structures but lacking cytokine-inducing capacity (like PE-4) may be of relevance for their function as potent antagonists of LPS in therapy of endotoxic shock and sepsis. </jats:p>",
  "DOI": "10.1177/096805199400100104",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2008,
        1,
        25
      ]
    ],
    "date-time": "2008-01-25T19:57:02Z",
    "timestamp": 1201291022000
  },
  "page": "14-20",
  "source": "Crossref",
  "is-referenced-by-count": 20,
  "title": "Inhibition of LPS binding on human monocytes by phosphonooxyethyl analogs of lipid A",
  "prefix": "10.1177",
  "volume": "1",
  "author": [
    {
      "given": "H.",
      "family": "Heine",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Immunology and Cell Biology, Institut fur Experimentelle Biologie und Medizin, Borstel, Germany, Department of Immunochemistry and Biochemical Microbiology, Forschungsinstitut Borstel, Institut f\u00fcr Experimentelle Biologie und Medizin, Borstel, Germany, Department of Chemistry, Osaka University, Faculty of Science, Osaka, Japan, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan"
        }
      ]
    },
    {
      "given": "H.",
      "family": "Brade",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Immunology and Cell Biology, Institut fur Experimentelle Biologie und Medizin, Borstel, Germany, Department of Immunochemistry and Biochemical Microbiology, Forschungsinstitut Borstel, Institut f\u00fcr Experimentelle Biologie und Medizin, Borstel, Germany, Department of Chemistry, Osaka University, Faculty of Science, Osaka, Japan, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan"
        }
      ]
    },
    {
      "given": "S.",
      "family": "Kusumoto",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Immunology and Cell Biology, Institut fur Experimentelle Biologie und Medizin, Borstel, Germany, Department of Immunochemistry and Biochemical Microbiology, Forschungsinstitut Borstel, Institut f\u00fcr Experimentelle Biologie und Medizin, Borstel, Germany, Department of Chemistry, Osaka University, Faculty of Science, Osaka, Japan, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan"
        }
      ]
    },
    {
      "given": "T.",
      "family": "Kusama",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Immunology and Cell Biology, Institut fur Experimentelle Biologie und Medizin, Borstel, Germany, Department of Immunochemistry and Biochemical Microbiology, Forschungsinstitut Borstel, Institut f\u00fcr Experimentelle Biologie und Medizin, Borstel, Germany, Department of Chemistry, Osaka University, Faculty of Science, Osaka, Japan, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan"
        }
      ]
    },
    {
      "given": "E. Th.",
      "family": "Rietschel",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Immunology and Cell Biology, Institut fur Experimentelle Biologie und Medizin, Borstel, Germany, Department of Immunochemistry and Biochemical Microbiology, Forschungsinstitut Borstel, Institut f\u00fcr Experimentelle Biologie und Medizin, Borstel, Germany, Department of Chemistry, Osaka University, Faculty of Science, Osaka, Japan, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan"
        }
      ]
    },
    {
      "given": "H.-D.",
      "family": "Flad",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Immunology and Cell Biology, Institut fur Experimentelle Biologie und Medizin, Borstel, Germany, Department of Immunochemistry and Biochemical Microbiology, Forschungsinstitut Borstel, Institut f\u00fcr Experimentelle Biologie und Medizin, Borstel, Germany, Department of Chemistry, Osaka University, Faculty of Science, Osaka, Japan, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan"
        }
      ]
    },
    {
      "given": "A.J.",
      "family": "Ulmer",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Immunology and Cell Biology, Institut fur Experimentelle Biologie und Medizin, Borstel, Germany, Department of Immunochemistry and Biochemical Microbiology, Forschungsinstitut Borstel, Institut f\u00fcr Experimentelle Biologie und Medizin, Borstel, Germany, Department of Chemistry, Osaka University, Faculty of Science, Osaka, Japan, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan"
        }
      ]
    }
  ],
  "member": "179",
  "published-online": {
    "date-parts": [
      [
        1994,
        3,
        1
      ]
    ]
  },
  "reference": [
    {
      "key": "atypb1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/978-3-642-76412-7_16"
    },
    {
      "key": "atypb2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/scientificamerican0892-54"
    },
    {
      "key": "atypb3",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0171-2985(89)80036-1"
    },
    {
      "key": "atypb4",
      "first-page": "73",
      "volume": "89",
      "author": "Feist W.",
      "year": "1992",
      "journal-title": "Microbiol Immunol"
    },
    {
      "key": "atypb5",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)55023-7"
    },
    {
      "key": "atypb6",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/352342a0"
    },
    {
      "key": "atypb7",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/eji.1830161013"
    },
    {
      "key": "atypb8",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/IAI.57.4.1336-1338.1989"
    },
    {
      "key": "atypb9",
      "first-page": "23",
      "volume": "11",
      "author": "Wang M-H.",
      "year": "1992",
      "journal-title": "Lymphokine Cytokine Res"
    },
    {
      "journal-title": "FASEB J",
      "year": "1993",
      "author": "Rietschel E Th",
      "key": "atypb10"
    },
    {
      "key": "atypb11",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/IAI.61.6.2325-2333.1993"
    },
    {
      "key": "atypb12",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.172.1.77"
    },
    {
      "key": "atypb13",
      "doi-asserted-by": "crossref",
      "first-page": "3229",
      "DOI": "10.4049/jimmunol.142.9.3229",
      "volume": "142",
      "author": "Loppnow H.",
      "year": "1989",
      "journal-title": "J Immunol"
    },
    {
      "key": "atypb14",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0171-2985(11)80346-3"
    },
    {
      "key": "atypb15",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/IAI.58.11.3743-3750.1990"
    },
    {
      "key": "atypb16",
      "unstructured": "Loppnow H., Rietschel E Th, Brade H. et al. Lipid A precursor Ia (compound 406) and Rhodobacter capsulatus lipopolysaccharide: potent endotoxin antagonists in the human system in vitro . In: Levin J, Alving CR, Munford RS, St\u00fctz PL, eds. Bacterial endotoxin: recognition and effector mechanisms. Amsterdam: Elsevier 1993: 337-348."
    },
    {
      "key": "atypb17",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/IAI.60.12.5145-5152.1992"
    },
    {
      "key": "atypb18",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0171-2985(11)80338-4"
    },
    {
      "key": "atypb19",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.176.2.485"
    },
    {
      "key": "atypb20",
      "doi-asserted-by": "publisher",
      "DOI": "10.1248/cpb.38.3366"
    },
    {
      "key": "atypb21",
      "doi-asserted-by": "publisher",
      "DOI": "10.1248/cpb.39.1994"
    },
    {
      "key": "atypb22",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/IAI.60.8.3309-3314.1992"
    },
    {
      "key": "atypb23",
      "first-page": "226",
      "volume": "243",
      "author": "Galanos C.",
      "year": "1979",
      "journal-title": "Zentralbl Bakt Hyg A"
    },
    {
      "key": "atypb24",
      "doi-asserted-by": "publisher",
      "DOI": "10.1246/bcsj.60.2205"
    },
    {
      "key": "atypb25",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0171-2985(84)80042-X"
    },
    {
      "key": "atypb26",
      "first-page": "165",
      "volume": "4",
      "author": "Earle W.R.",
      "year": "1943",
      "journal-title": "J Natl Cancer Inst"
    },
    {
      "key": "atypb27",
      "doi-asserted-by": "crossref",
      "first-page": "3505",
      "DOI": "10.4049/jimmunol.148.11.3505",
      "volume": "148",
      "author": "Heumann D.",
      "year": "1992",
      "journal-title": "J Immunol"
    },
    {
      "key": "atypb28",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0171-2985(11)80340-2"
    },
    {
      "key": "atypb29",
      "doi-asserted-by": "publisher",
      "DOI": "10.1096/fasebj.5.12.1916089"
    },
    {
      "key": "atypb30",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0165-2478(93)90096-K"
    },
    {
      "key": "atypb31",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0952-7915(91)90082-C"
    },
    {
      "key": "atypb32",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0167-5699(93)90212-4"
    },
    {
      "key": "atypb33",
      "doi-asserted-by": "crossref",
      "first-page": "547",
      "DOI": "10.4049/jimmunol.141.2.547",
      "volume": "141",
      "author": "Haziot A.",
      "year": "1988",
      "journal-title": "J Immunol"
    },
    {
      "key": "atypb34",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1698311"
    },
    {
      "key": "atypb35",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2402637"
    },
    {
      "key": "atypb36",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.170.4.1231"
    },
    {
      "key": "atypb37",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0065-2776(08)60502-7"
    }
  ],
  "container-title": "Journal of Endotoxin Research",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.sagepub.com/doi/pdf/10.1177/096805199400100104",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://journals.sagepub.com/doi/pdf/10.1177/096805199400100104",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2025,
        3,
        1
      ]
    ],
    "date-time": "2025-03-01T18:04:10Z",
    "timestamp": 1740852250000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.sagepub.com/doi/10.1177/096805199400100104"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1994,
        3
      ]
    ]
  },
  "references-count": 37,
  "journal-issue": {
    "issue": "1",
    "published-print": {
      "date-parts": [
        [
          1994,
          3
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1177/096805199400100104"
  ],
  "URL": "http://dx.doi.org/10.1177/096805199400100104",
  "relation": {},
  "ISSN": [
    "0968-0519"
  ],
  "subject": [],
  "container-title-short": "Journal of Endotoxin Research",
  "published": {
    "date-parts": [
      [
        1994,
        3
      ]
    ]
  }
}