Conclusion
Recognition of LPS, one of the most potent prokaryotic stimulators of immune and non-immune cells of higher organisms, appears to be a complex and highly differentiated process. In CD14-positive cells a model involving two major elements for LPS recognition and uptake, i.e. LBP and cellular CD14, is becoming apparent. The involvement of LBP in the stimulation of CD14-negative cells, such as EC or SMC remains unclear, whereas in this case sCD14 appears to be the acceptor of LPS. In Fig. 2 these considerations are summarized in a simplified model. For both CD14-positive and CD14-negative cell systems, an as-yet-undefined membrane-associated receptor has been postulated, transducing the “endotoxin” signal into the cell. Further work is necessary to define this signal transduction protein and to ultimately clarify the cellular LPS recognition mechanism. The molecular characterization of LPS-binding, -transport and -signaling events will hopefully lead to long-awaited, and effective novel intervention strategies in endotoxemia and Gramnegative septic shock.
Similar content being viewed by others
References
Akeson AL, Mosher LB, Woods CW, Schröder KK, Bowlin TL (1992) Human aortic endothelial cells express the type I but not the type II receptor for interleukin 1 (IL-1). J Cell Physiol 153:583–588
Anderson J, Melchers F, Galanos C, Lüderitz O (1973) The mitogenic effect of LPS on bone marrow derived mouse lymphocytes. Lipid A as the mitogenic part of the molecule. J Exp Med 137:943–953
Arditi M, Zhou J, Dorio R, Rong GW, Goyert SM, Kim KS (1993) Endotoxin-mediated endothelial cell injury and activation: role of soluble CD14. Infect Immun 61:3149–3156
Ball E, Graziano RF, Shen L, Fanger MW (1982) Monoclonal antibodies to novel myeloid antigens reveal human granulocyte heterogeneity. Proc Natl Acad Sci USA 79:5374–5378
Ball ED, Guyre PM, Shen L, Fanger MW, Baker PE, Maliszewski CR, Glynn JM (1984) Gamma interferon induces monocytoid differentiation in the HL60 cell line. J Clin Invest 73:1072–1077
Baumann H, Wong GG (1989) Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. J Immunol 143:1163–1170
Bazil V, Horejsi B, Baudys M, Kristofova H, Strominger JL, Kostka W, Hilgert I (1986) Biochemical characterization of soluble form of the 53-kDa monocyte surface antigen. Eur J Immunol 16:1583–1589
Bazil V, Strominger JL (1991) Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes. J Immunol 147:1567–1574
Beasley D, Cohen RA, Levinsky NG (1990) Endotoxin inhibits contraction of vascular smooth muscle in vitro. Am J Physiol 258:H1187-H1190
Berger D, Beger HD (1988) Quantification of the endotoxin-binding capacity of human transferrin. In: Levin J, Ten Kate JW, Büller HR, van Deventer SJH, Sturk A (eds) Bacterial endotoxins: pathophysiological effects, clinical significance, and pharmacological control. Liss, New York, pp 115–124
Bond RF (1993) Peripheral macro and microcirculation. In: Schlag G, Redl H (eds), Pathophysiology of shock, sepsis and organ failure. Springer-Verlag, Berlin Heidelberg New York, pp 893–907
Bond RF, Scott CG, Krech LH, Bond CH (1990) Systematic and local effects of endotoxin on canine gracilis muscle vascular conductance. Am J Physiol 258:H1498-H1506
Boraschi D, Rambaldi A, Sica A, Ghiara P, Colotta F, Wang JM, de Rossi M, Zoia C, Remuzzi G, Bussolino F, Scapigliat G, Stoppacciaro A, Ruco L, Tagliabue A, Mantovani A (1991) Endothelial cells express the interleukin 1 receptor type I. Blood 78:1262–1267
Brade L, Bessler W, Brade H (1988) Mitogenic activities of synthetic Escherichia coli lipid A and a synthetic partial sturcture (tripalmitoyl pentapeptide) of E. coli lipoprotein. Infect Immun 56:1382–1384
Brade L, Brade H (1985) A 28 000-dalton protein of normal mouse serum binds specifically to the inner core region of bacterial lipopolysaccharide. Infect Immun 50:687–694
Brandenburg K, Mayer H, Koch MHJ, Weckesser J, Rietschel ET, Seydel U (1993) Influence of the supramolecular structure of free lipid A on its biological activity. Eur J Biochem 218:555–563
Bussolino F, Breviario F, Tetta C, Aglietta M, Mantovani A, Dejana E (1986) Interleukin 1 stimulates platelet-activating factor production in cultured human endothelial cells. J Clin Invest 77:2027–2033
Calvo F, Martin PM, Jabrane N, De Cremoux R, Magdelenat H (1987) Human breast cancer cells share antigens with the myeloid monocyte lineage. Br J Cancer 65:15–19
Clinton SK, Underwood R, Hayes L, Sherman ML, Kufe DW, Libby P (1992) Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. Am J Pathol 140:301–316
Couturier C, Haeffner-Cavaillon N, Caroff MM, Kazatchkine M (1991) Binding sites for endotoxin (lipopolysaccharides) on human monocytes. J Immunol 147:1899–1904
Cushing SD, Berliner JA, Valente AJ, Territo MC, Navab M, Parhami F, Gerrity R, Schwartz CJ, Fogelman AM (1990) Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial and smooth muscle cells. Proc Natl Acad Sci USA 87:5134–5138
Dahinden C, Galanos C, Fehr J (1983) Granulocyte activation by endotoxin: correlation between adherence and other granulocyte functions, and the role of endotoxin structure on biologic activity. J Immunol 130:857–868
Day JR, Albers JJ, Lofton-Day CE, Gilbert TL, Ching AFT, Grant FJ, O'Hara PJ, Marcovina SM, Adolphson JL (1994) Complete cDNA encoding human phospholipid transfer protein from human endothelial cells. J Biol Chem 269:9388–9391
Drayna D, Kohr W, Henzel W, McLean J, Jarnagin AS, Fielding C, Law R (1987) Cloning and sequencing of human cholesterolester transfer protein cDNA. Nature 327:632–634
Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA (1986) Induction by IL-1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 137:245–254
Dziarski R (1994) Cell-bound albumin is the 70-kDa peptidoglycan, lipopolysaccharide, and lipoteichoic acid binding protein on lymphocytes and macrophages. J Biol Chem 269:20431–20436
Eisbach P, Weiss J (1993) Bactericidal/permeability increasing protein and host defense against Gram-negative bacteria and endotoxin. Curr Opin Immunol 5:103–107
Erwin AL, Mandrell RE, Munford RS (1991) Enzymatically deacylated Neisseria lipopolysaccharide (LPS) inhibits murine splenocyte mitogenesis induced by LPS. Infect Immun 59:1881–1887
Ezekowitz RAB, Day LE, Herman G (1988) A human mannose-binding protein is an acute-phase reactant that shares sequence homology with other vertebrate lectins. J Exp Med 167:1034–1046
Flad H-D, Loppnow H, Rietschel ET, Ulmer AJ (1993) Agonists and antagonists for lipopolysaccharide-induced cytokines. Immunobiology 187:303–316
Flegel WA, Wölpl A, Mannel DN, Northoff H (1989) Inhibition of endotoxin-induced activation of human monocytes by human lipoproteins. Infect Immun 57:2237–2245
Franklin WA, Mason DY, Pulford K, Falini B, Bliss E, Gatter KC, Stein H, Clarke LC, McGhee JO (1986) Immunohistological analysis of human mononuclear phagocytes and dendritic cell by using monoclonal antibodies. Lab Invest 54:322–335
Freudenberg MA, Bog-Hansen TC, Back U, Galanos C (1980) Interaction of lipopolysaccharides with plasma high density lipoproteins in rats. Infect Immun 28:373–380
Frey EA, Miller DS, Jahr TG, Sundan A, Bazil V, Espevik T, Finlay BB, Wright SD (1992) Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med 176:1665–1671
Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376
Galanos C, Lüderitz O, Rietschel ET, Westphal O, Brade H, Brade L, Freudenberg M, Schade U, Imoto M, Yoshimura H, Kusumoto S, Shiba T (1985) Synthetic and natural E. coli free lipid A express identical endotoxic activities. Eur J Biochem 148:1–5
Gallay P, Heumann D, Le RD, Barras C, Glauser MP (1993) Lipopolysaccharide-binding protein as a major plasma protein responsible for endotoxemic shock. Proc Natl Acad Sci USA 90:9935–9938
Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H (1987) Interferon-β2/BSF-2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute-phase protein response in liver cells. Proc Natl Acad Sci USA 84:7251–7255
Gazzano-Santoro H, Meszaros K, Birr C, Carroll SS, Theofan G, Horwitz AH, Lim E, Aberle S, Kasler H, Parent JB (1994) Competition between rBPI23, a recombinant fragment of bactericidal/permeability increasing protein, and lipopolysaccharide (LPS)-binding protein for binding to LPS and Gram-negative bacteria. Infect Immun 62:1185–1191
Geng JG, Bevilaqua MP, Moore KL, McIntyre TM, Prescott SM, Kim JM, Bliss GA, Zimmerman GA, McEver RP (1990) Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature 343:757–760
Goldblum SE, Brann TW, Ding X, Pugin J, Tobias PS (1994) Lipopolysaccharide (LPS)-binding protein and soluble CD14 function as accessory molecules for LPS-induced changes in endothelial barrier function, in vitro. J Clin Invest 93:692–702
Golenbock DT, Hampton RY, Qureshi N, Takayama K, Raetz CRH (1991) Lipid A-like molecules that antagonize the effects of endotoxins of human monocytes. J Biol Chem 266:19490–19498
Golenbock DT, Liu Y, Millham FH, Freeman MW, Zoeller RA (1993) Surface expression of human CD14 in Chinese hamster ovary fibroblasts imparts macrophage-like responsiveness to bacterial endotoxin. J Biol Chem 268:22055–22059
Goyert SM, Ferrero E, Rettig WJ, Yenamandra AK, Obata F, LeBeau MM (1988) The CD14 monocyte differentiation antigen maps to a region encoding growth factors and receptors. Science 239:497–500
Gray PW, Flaggs G, Leong SR, Gumina RJ, Weiss J, Ooi CE, Elsbach P (1989) Cloning of the cDNA of a human neutrophil bactericidal protein. Structural and functional correlations. J Biol Chem 264:9505–9509
Griffin JD, Ritz J, Nadler LM, Schlossman SF (1981) Expression of myeloid differentiation antigens on normal and malignant cells. J Clin Invest 68:932–941
Haeffner-Cavaillon N, Caroff M, Cavaillon H-M (1989) Interleukin 1 induction by lipopolysaccharide: structural requirement of the 3-deoxy-d-manno-2-octulosonic acid. Mol Immunol 26:485–494
Hampton RY, Golenbock DT, Penman M, Krieger M, Raetz CRH (1991) Recognition and plasma clearance of endotoxin by scavenger receptors. Nature 352:342–344
Han J, Lee JD, Tobias PS, Ulevitch RJ (1993) Endotoxin induces rapid protein tyrosine phosphorylation in 70Z/3 cells expressing CD14. J Biol Chem 268:25009–25014
Hara-Kuge S, Amano F, Nishijima M, Akamatsu Y (1990) Isolation of an LPS-resistant mutant, with defective LPS-binding of cultured macrophage-like cells. J Biol Chem 265:6606–6610
Harlan JM, Harker LA, Reidy MA, Gajdusek CM, Schwartz SM, Striker GE (1983) Lipopolysaccharide-mediated bovine endothelial cell injury in vitro. Lab Invest 48:269–274
Haziot A, Chan S, Ferrero E, Low MG, Silber R, Goyert SM (1988) The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J Immunol 141:547–552
Haziot A, Rong GW, Silver J, Goyert SM (1993) Recombinant soluble CD14 mediates the activation of endothelial cells by lipopolysaccharide. J Immunol 151:1500–1507
Hoess A, Watson S, Siber GR, Liddington R (1993) Crystal structure of an endotoxin-neutralizing protein from horseshoe crab, Limulus anti-LPS factor, at 1.5 Å resolution. EMBO J 12:3351–3356
Hohmann HP, Brockhaus M, Bäuerle PA, Remy R, Kolbeck R, van Loon AP (1990) Expression of types A and B tumor necrosis factor (TNF) receptors is independently regulated, and both receptors mediate activation of the transcription factor NF-κB. J Biol Chem 265:22409–22417
Holst O, Brade H (1992) Chemical structure of the core region of lipopolysaccharides. In: Morrison DC, Ryan JL (eds) Bacterial endotoxic lipopolysaccharides, vol 1. CRC Press, Boca Raton, pp 136–170
Ihara I, Harada Y, Ihara S, Kawakami M (1982) A new complement-dependent bacterial factor found in nonimmune mouse sera. J Immunol 128:1256–1260
Johnson KJ, Ward P, Goralnick BS, Osborn MJ (1977) Isolation from human serum of an inactivator of bacterial lipopolysaccharide. Am J Pathol 88:559–574
Kirikae T, Kirikae F, Schade FU, Yoshida M, Kondo S, Hisatsune K, Nishikawa S-I, Rietschel ET (1991) Detection of lipopolysaccharide-binding proteins on membranes of murine lymphocyte and macrophage-like cell lines. FEMS Microbiol Immunol 76:327–336
Kirkland TN, Finley F, Leturq D, Moriarty A, Lee JD, Ulevitch RJ, Tobias PS (1993) Analysis of lipopolysaccharide binding by CD14. J Biol Chem 268:24818–24823
Kirkland TN, Virca GD, Kuus-Reichel T, Multer FK, Kim SY, Ulevitch RJ, Tobias PS (1990) Identification of lipopolysaccharide-binding proteins in 70/Z3 cells by photoaffinity cross-linking. J Biol Chem 265:9520–9525
Kodama T, Freeman M, Rohrer L, Zablecky J, Matsudaira P, Krieger M (1990) Type I macrophage scavenger receptor contains a-helical and collagen-like coiled coils. Nature 343:531–535
Kovach NL, Yee E, Munford RS, Raetz CRH, Harlan JM (1990) Lipid IVa inhibits synthesis and release of tumor necrosis factor induced lipopolysaccharide in human blood ex vivo. J Exp Med 172:77–84
Krauss JH, Seydel U, Weckesser J, Mayer H (1989) Structural analysis of the nontoxic lipid A of Rhodobacter capsulatus 37b4. Eur J Biochem 180:519–526
Krüger C, Schütt C, Obertacke U, Joka T, Müller FE, Knöller J, Köhler M, König W, Schönfeld W (1991) Serum CD14 levels in polytraumatized and severely burned patients. Clin Exp Immunol 85:297–301
Labeta MO, Landmann R, Orbrecht JP, Obrist R (1991) Human B cells express membrane-bound and soluble forms of CD14 myeloid antigen. Mol Immunol 289:115–122
Lauener RP, Geha RS, Vercelli D (1990) Engagement of the monocyte surface antigen CD14 induces lymphocytic function-associated antigen-1/intercellular adhesion molecule-1-dependent homotypic adhesion. J Immunol 145:1390–1394
Lee JD, Kato K, Tobias PS, Kirkland TN, Ulevitch RJ (1992) Transfection of CD14 into 70Z/3 cells dramatically enhances the sensitivity to complexes of lipopolysaccharide (LPS) binding protein. J Exp Med 175:1697–1705
Lei MG, Stimpson SA, Morrison DC (1991) Specific endotoxic lipopolysaccharide-binding receptors on murine splenocytes: III. Binding specificity and characterization. J Immunol 147:1925–1932
Li H, Cybulski MI, Gimbrone MA, Jr, Libby P (1993) Inducible expression of vascular cell adhesion molecule-1 by vascular smooth muscle cells in vitro and within rabbit atheromata. Am J Pathol 143:1551–1559
Libby P, Ordovas JM, Auger KR, Robbins H, Birinyi LK, Dinarello CA (1986) Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. Am J Pathol 124:179–186
Libby P, Ordovas JM, Birinyi LK, Auger KR, Dinarello CA (1986) Inducible interleukin-1 expression in human vascular smooth muscle cells. J Clin Invest 78:1432–1438
Linares HA (1993) Sepsis related renal morphological alterations and the functional correlates. In: Schlag G, Redl H (eds) Pathophysiology of shock, sepsis and organ failure. Springer-Verlag, Berlin Heidelberg, pp 961–972
Lindberg AA (1977) Bacterial surface carbohydrates and bacteriophage adsorption. In: Sutherland IW (ed) Surface carbohydrates of the procariotic cell. Academic Press, New York, p 289
Loos M, Euteneuer B, Clas F (1990) Interaction of bacterial endotoxin (LPS) with fluid phase and macrophage membrane associated C1q, the Fc-recognizing component of the complement system. Adv Exp Med Biol 256:301–317
Loppnow H (1994) LPS and vascular cell-derived IL-1 activate vascular cells by specific mechanisms. In: Levin J, van Deventer SJH, van der Poll T, Sturk A (eds) Bacterial endotoxins: basic science to anti-sepsis strategies. Wiley, New York, pp 309–321
Loppnow H, Brade H, Dürrbaum I, Dinarello CA, Kusumoto S, Rietschel ET, Flad HD (1989) IL-1 induction capacity of defined lipopolysaccharide partial structure. J Immunol 142:3229–3238
Loppnow H, Brade L, Brade H, Rietschel ET, Kusumoto S, Shiba T, Flad HD (1986) Induction of human interleukin-1 by bacterial and synthetic lipid A. Eur J Immunol 16:1263–1267
Loppnow H, Flad HD, Rietschel ET, Brade H (1993) The active principle of bacterial lipopolysaccharides (endotoxins) for cytokine induction. In: Schlag G, Redl H (eds) Pathophysiology of shock, sepsis and organ failure. Springer, Berlin Heidelberg New York, pp 405–416
Loppnow H, Lippy P (1989) Adult human vascular endothelial cells express the IL-6 gene differentially in response to LPS or IL-1. Cell Immunol 122:493–503
Loppnow H, Libby P (1990) Proliferating or Interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6. J Clin Invest 85:731–738
Loppnow H, Libby P (1992) Functional significance of human vascular smooth muscle cell-derived interleukin 1 in paracrine and autocrine regulation pathways. Exp Cell Res 198:283–290
Loppnow H, Libby P, Freudenberg MA, Krauss JH, Weckesser J, Mayer H (1990) Cytokine induction by LPS corresponds to lethal toxicity and is inhibited by “non-toxic” Rhodobacter capsulatus LPS. Infect Immun 58:3743–3750
Loppnow H, Rietschel ET, Brade H, Schönbeck U, Libby P, Wang MH, Heine H, Feist W, Dürrbaum-Landmann I, Ernst M, Brandt E, Grage-Griebenow E, Ulmer AJ, Campos-Portugez S, Schade U, Kirikae T, Kusumoto S, Krauss J, Mayer H, Flad HD (1993) 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 receptor mechanisms. Elsevier Science Publishers, Amsterdam, pp 337–348
Loppnow H, Schönbeck U, Stelter F, Schlüter C, Ernst M, Schütt C, Flad HD (1994) Endotoxin activates human vascular smooth muscle cells despite lack of expression of CD14 mRNA or endogenous membrane CD14. Infect Immun (in press)
Lüderitz O, Westphal O, Staub AM, Nikaido H (1971) Isolation and chemical and immunological characterization of bacterial lipopolysaccharides. In: Weinbaum G, Kadis S, Ajl SJ (eds) Microbial toxins. Academic Press, New York, pp 145–233
Mackievicz A, Ganapathi MK, Shultz D, Brubenec A (1990) Transforming growth factor β1 regulates production of acute phase proteins. Proc Natl Acad Sci USA 87:1491–1495
Maliszewski CR (1991) CD14 and immune response to lipopolysaccharide. Science 252:1321–1322
Maliszewski CR, Ball ED, Graziano RF, Fanger MW (1985) Isolation and characterization of My23, a myeloid cell-derived antigen reactive with the monoclonal antibody AML-2–23. J Immunol 135:1929–1936
Marra MN, Wilde CG, Collins MS, Snable JL, Thornton MB, Scott RW (1992) The role of bactericidal/permeability-increasing protein as a natural inhibitor of bacterial endotoxin. J Immunol 148:532–537
Mathison J, Wolfson E, Steinemann S, Tobias P, Ulevitch R (1993) Lipopolysaccharide (LPS) recognition in macrophages. Participation of LPS-binding protein and CD14 in LPS-induced adaptation in rabbit peritoneal exudate macrophages. J Clin Invest 92:2053–2059
Mathison JC, Wolfson E, Ulevitch RJ (1988) Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits. J Clin Invest 81:1925–1937
Mattern T, Tannhäuser A, Reiling N, Toellner K-M, Duchrow M, Kusumoto S, Rietschel ET, Ernst M, Brade H, Flad H-D, Ulner AJ (1994) Endotoxin and lipid A stimulate proliferation of human T-cells in the presence of autologous monocytes. J Immunol 153:2996–3004
Morabito F, Prasthofer EF, Dunlap NE, Grossi CE, Tilden AB (1987) Expression of myelomonocytic antigens on chronic lymphocytic leukemia B cells correlates with their ability to produce interleukin 1. Blood 70:1750–1757
Nathan CF (1987) Secretory products of macrophages. J Clin Invest 79:319–323
Navab M, Hough GP, Van Lenten BJ, Berliner JA, Fogelman AM (1988) Low density lipoproteins transfer bacterial lipopolysaccharides across endothelial monolyers in a biologically active form. J Clin Invest 81:601–605
Nawroth PP, Handley DA, Esmon CT, Stern DM (1986) Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci USA 48:3460–3464
Nestle FO, Zheng XG, Thompson CB, Turka LA, Nickoloff BJ (1993) Characterization of dermal dendritic cells obtained from normal human skin reveals phenotypic and functionally distinctive subsets. J Immunol 151:6535–6545
Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, Lobb R (1989) Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 59:1203–1211
Osborn MJ (1979) Biosynthesis and assembly of lipopolysaccharide of the outer membrane. In: Inouye M (ed) Bacterial outer membranes, biogenesis and functions. Wiley, New York, p 15
Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526
Patrick D, Betts J, Frey EA, Prameya R, Dorovini-Zis K, Finlay BB (1992) Haemophilus influenzae lipopolysaccharide disrupts confluent monolayers of bovine brain endothelial cells via a serum-dependent cytotoxic pathway. J Infect Dis 165:865–872
Perlmutter DH, Dinarello CA, Punsal PI, Colten HR (1986) Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest 78:1349–1354
Pober JS, Cotran RS (1990) Cytokines and endothelial cell biology. Physiol Rev 70:427–451
Pober JS, Gimbrone MA, Jr, Lapierre LA, Mendrick DL, Fiers W, Rothlein R, Springer TA (1986) Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol 137:1893–1896
Pohlman TH, Harlan JM (1992) Endotoxin endothelial cell interactions. In: Ryan JL, Morrison DC (eds) Bacterial endotoxic lipopolysaccharides, vol 1. Molecular biochemistry and cellular biology. CRC Press, Boca Raton, pp 347–371
Pohlman RTH, Munford RS, Harlan JM (1987) Deacylated lipopolysaccharide inhibits neutrophil adherence to endothelium induced by lipopolysaccharide in vitro. J Exp Med 165:1393–1402
Pugin J, Schürer-Maly CC, Leturcq D, Moriarty A, Ulevitch RJ, Tobias PS (1993) Lipopolysaccharide activation of human endothelial and epithelial cells is mediated by lipopolysaccharide-binding protein and soluble CD14. Proc Natl Acad Sci USA 90:2744–2748
Quesenberry PJ, Gimbrone MA, Jr (1980) Vascular endothelium as a regulator of granulopoiesis: production of colony-stimulating activity by cultured human endothelial cells. Blood 56:1060–1067
Raetz CRH (1990) Biochemistry of endotoxins. Annu Rev Biochem 59:129–170
Rapolee DA, Werb Z (1992) Macrophage derived growth factors. Curr Top Microbiol Immunol 181:87–140
Read MA, Cordle SR, Veach RA, Carlisle CD, Hawiger J (1993) Cell-free pool of CD14 mediates activation of transcription factor NF-κB by lipopolysaccharide in human endothelial cells. Proc Natl Acad Sci USA 90:9887–9891
Reidy MA, Bowyer D (1977) Scanning electron microscopy: morphology of aortic endothelium following injury by endotoxin and during subsequent repair. Atheriosclerosis 26:319–328
Rice GE, Munro JM, Bevilacqua MP (1990) Inducible cell adhesion molecule 110 (IN-CAM-110) is an endothelial receptor for lymphocytes. A CD11/CD18-independent adhesion mechanism. J Exp Med 171:1369–1375
Riedo FX, Munford RS, Campbell WB, Reisch JS, Chien KR, Gerard RD (1990) Deacylated lipopolysaccharide inhibits plasminogen activator inhibitor-1, prostacyclin, and prostaglandin E2 production by lipopolysaccharide but not by tumor necrosis factor. J Immunol 144:3506–3512
Rietschel ET, Brade H (1992) Bacterial endotoxins. Sci Am 267:54–61
Rietschel ET, Brade L, Lindner B, Zähringer U (1992) Biochemistry of lipopolysaccharides. In: Ryan JL, Morrison DC (eds) Bacterial endotoxic lipopolysaccharides, vol 1. Molecular biochemistry and cellular biology. CRC Press, Boca Raton, pp 4–41
Rietschel ET, Kirikae T, Schade FU, Mamat U, Schmidt G, Loppnow H, Ulmer AJ, Zähringer U, Seydel U, di Padova F, Schreier M, Brade H (1994) Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J 8:217–225
Robinson PJ (1991) Phosphatidylinositol membrane anchors and T-cell activation. Immunol Today 12:35–41
Rollins BJ, Yoshimura T, Leonard EJ, Pober JS (1990) Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am J Pathol 136:1229–1233
Root RK, Jacobs R (1991) Septicemia and septic shock. In: Wilson J, et al. (eds) Principles of internal medicine, 12th ed. McGraw Hill, New York, pp 502–516
Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony stimulating factor plus IL-4 and down-regulated by TNFα. J Exp Med 179:1109–1118
Salvemini D, Korbut R, Anggard E, Vane J (1990) Immediate release of nitric oxide-like factor from bovine endothelial cells by Escherichia coli lipopolysaccharide. Proc Nat Acad Sci USA 87:2593–2597
Schade UF, Burmeister J, Elekes E, Engel R, Wolter DT (1989) Mononuclear phagocytes and eicosanoids: aspects of their synthesis and biological activities. Blut 59:475–485
Schletter J, Brade H, Krüger C, Loppnow H, Rietschel ET, Flad HD, Ulmer AJ (1994) Binding of lipopolysaccharide to an 80 kDa membrane protein of human cells is mediated by serum factors. Immunobiology 191:273
Schönbeck U, Brandt E, Petersen F, Flad HD, Loppnow H (1995) Interleukin 8 specifically binds to endothelial cells but not to smooth muscle cells. J Immunol (in press)
Schönbeck U, Flad HD, Rietschel ET, Brandt E, Loppnow H (1994) S-form LPS induces leukocyte adhesion to human vascular endothelial cells as potent as IL-1: lipid A precursor Ia antagonizes induction of adhesion by LPS. J Endotox Res 1:4–13
Schumann RR (1992) Function of lipopolysaccharide (LPS)-binding protein (LBP) and CD14, the receptor for LPS/LBP complexes: a short review. Res Immunol 143:11–15
Schumann RR, Herrmann F (1994) The macrophage — a tissue specific defense cell: origin, diversity and function. Focus growth factors 5:1–5
Schumann RR, Kirschning C, Unbehaun A, Aberle H, Knopf HP, Lamping N, Seilhamer J, Ulevitch RJ, Herrmann F (1995) Identification of lipopolysaccharide binding protein as a novel acute phase protein (in press)
Schumann RR, Lamping N, Kirschning C, Knopf HP, Hoess A, Herrmann F (1994) Lipopolysaccharide binding protein: its role and therapeutic potential in inflammation and sepsis. Biochem Soc Transact 22:80–83
Schumann RR, Leong SR, Flaggs GW, Gray PW, Wright SD, Mathison JC, Tobias PS, Ulevitch RJ (1990) Structure and function of lipopolysaccharide binding protein. Science 249:1429–1431
Schütt C, Ringel B, Nausch M, Bazil V, Horejsi V, Neels P, Valzel H, Jonas L, Siegl E, Friemel H, Plantikow A (1988) Human monocyte activation induced by an anti-CD14 monoclonal antibody. Immunol Lett 19:321–328
Schütt C, Schilling T, Grunwald U, Schönfeld W, Krüger C (1992) Endotoxin-neutralizing capacity of soluble CD14. Res Immunol 143:71–78
Schütt C, Schilling T, Krüger C (1991) sCD14 prevents endotoxin inducible oxidative burst response of human monocytes. Allergy Immunol 37:159–164
Seydel U, Brandenburg K, Rietschel ET (1994) A case for an endotoxic conformation. In: Levin J, van Deventer SJH, van der Poll T, Sturk A (eds) Bacterial endotoxins: basic science to anti-sepsis strategies. Wiley, New York, pp 17–30
Shalaby MR, Waage A, Espevik T (1989) Cytokine regulation of interleukin 6 production by human endothelial cells. Cell Immunol 121:372–382
Strieter RM, Kunkel SL, Showell HJ, Remick DG, Phan SH, Ward PA, Marks RM (1989) Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science 243:1467–1469
Strunk RC, Whitehead AS, Cobe FS (1985) Pretranslation and regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopolysaccharide. J Clin Invest 76:985–990
Suttorp N, Flöer B, Schnittler H, Seeger W, Bhakti S (1990) Effect of E. coli hemolysin on endothelial cell function. Infect Immun 58:3796–3801
Suttorp N, Weber U, Welsch T, Schudt C (1993) Role of phosphodiesterases in the regulation of endothelial permeability in vitro. J Clin Invest 91:1421–1428
Thieme TR, Wagner CR (1989) The molecular weight of the endothelial cell IL-1 receptor is 78,000. Mol Immunol 26:249–252
Tobias PS, Mathison JC, Ulevitch RJ (1988) A family of lipopolysaccharide binding proteins involved in responses to gram-negative sepsis. J Biol Chem 263:13479–13481
Tobias PS, Soldau K, Ulevitch RJ (1986) Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J Exp Med 164:777–793
Ulevitch RJ (1993) Recognition of bacterial endotoxins by receptor-dependent mechanisms. Adv Immunol 53:267–289
Ulevitch RJ, Mathison CJ, Schumann RR, Tobias PS (1990) A new model of macrophage stimulation by bacterial lipopolysaccharide. J Trauma 30:189–191
Ulevitch RJ, R. JA, Weinstein DB (1979) New function for high density lipoproteins: Their participation in intravascular reactions of bacterial lipopolysaccharides (LPS). J Clin Invest 64:1516–1524
Ulevitch RJ, Tobias PS (1994) Recognition of endotoxin by cells leading to transmembrane signalling. Curr Opin Immunol 6:125–130
Vaara M, Nikaido H (1984) Molecular organization of the bacterial outer membrane. In: Proctor RA (ed) Handbook of endotoxin, vol 1. Elsevier, Amsterdam, p 1
Vane JR, Anggard EE, Botting RM (1990) Regulatory functions of the vascular endothelium. N Engl J Med 323:27–36
Von Asmuth EJU, Dentener MA, Bazil V, Bouma MG, Leeuwenberg JFM, Buurman WA (1993) Anti-CD14 antibodies reduce responses of cultured human endothelial cells to endotoxin. Immunology 80:78–83
Vosbeck K, Tobias P, Mueller H, Allen RA, Arfors KE, Ulevitch RJ, Sklar LA (1990) Priming of polymorphonuclear granulocytes by lipopolysaccharides and its complexes with lipopolysaccharide binding protein and high density lipoprotein. J Leukoc Biol 47:97–104
Wang JM, Sica A, Peri G, Walter S, Padura IM, Libby P, Ceska M, Colotta F, Mantovani A, Wang JM, Sica A, Peri G, Walter S, Padura IM, Libby P, Ceska M, Colotta F, Mantovani A (1991) Expression of monocyte chemotactic protein and interleukin 8 by cytokine-activated human vascular smooth muscle cells. Arterioscler Thromb 11:1166–1174
Warren JS, Kunkel SL, Cunningham TW (1988) Macrophage-derived cytokines amplify immune complex-triggered oxygen responses by rat alveolar macrophages. Am J Pathol 130:498–514
Weingarten R, Sklar LA, Mathison JC, Omidi S, Ainsworth T, Simon S, Ulevitch RJ, Tobias PS (1993) Interactions of lipopolysaccharide with neutrophils in blood via CD14. J Leukoc Biol 53:518–524
Weinstein SL, Gold MR, DeFranco AL (1991) Bacterial lipopolysaccharide stimulating protein tyrosine phosphorylation in macrophages. Proc Natl Acad Sci USA 88:4148–4152
Westphal O, Lüderitz O (1954) Chemische Erforschung von Lipopolysacchariden Gram-negativer Bakterien. Angew Chemie 66:407–417
Wollenweber HW, Seydel U, Lindner B, Lüderitz O, Rietschel ET (1984) Nature and location of amide-bound (R)-3-acyloxyacyl groups in lipid A of lipopolysaccharides from various Gram-negative bacteria. Eur J Biochem 145:265–272
Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding proteins. Science 249:1431–1433
Wright SD, Tobias PS, Ulevitch RJ, Ramos RA (1989) Lipopolysaccharide binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages. J Exp Med 170:1231–1241
Würfel M, Kunitake ST, Lichenstein H, Kane JP, Wright SD (1994) Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS. J Exp Med 180:1025–1035
Zähringer U, Lindner B, Rietschel ET (1994) Molecular structure of lipid A, the endotoxic center of bacterial lipopolysaccharides. Adv Carbohydr Chem Biochem 50:211–276
Ziegler-Heitbrock HWL, Passlick B, Flieger D (1988) The monoclonal antibody MY4 strains B lymphocytes and two distinct monocyte subsets in human peripheral blood. Hybridoma 7:521–527
Ziegler-Heitbrock HWL, Ulevitch RJ (1993) CD14: cell surface receptor and differentiation marker. Immunol Today 14:121–125
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schumann, R.R., Rietschel, E.T. & Loppnow, H. The role of CD14 and lipopolysaccharide-binding protein (LBP) in the activation of different cell types by endotoxin. Med Microbiol Immunol 183, 279–297 (1994). https://doi.org/10.1007/BF00196679
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00196679