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J Exp Med. 1995 April 1; 181(4): 1473–1479.
PMCID: PMC2191975

CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide


CD11c/CD18 is a member of the leukocyte integrin family, heterodimeric adhesion molecules that interact with a diverse repertoire of ligands, including bacterial lipopolysaccharide (LPS). Their role as signal transducing receptors remains uncertain. We used a heterologous expression system to determine if CD11c/CD18 was capable of initiating signal transduction in response to LPS-binding, as assessed by the induced translocation of nuclear factor-kappa B. We have previously reported that Chinese hamster ovary (CHO)-K1 fibroblasts, normally unresponsive to LPS, acquire serum-dependent macrophage-like responses to LPS when transfected with CD14 (Golenbock, D.T., Y. Liu, F. Millham, M. Freeman, and R. Zoeller. 1993. J. Biol. Chem. 268:22055-22059), a known LPS receptor. In contrast, CHO cells acquired serum-independent responses to Gram-negative bacteria and LPS when transfected with CD11c/CD18 (CHO/CD11c). In comparison to CHO cells transfected with CD14 (CHO/CD14), responses in CHO/CD11c cells were slower, required higher endotoxin concentrations for maximal response, and were not inhibited by the presence of antibodies to CD14. CD11c/CD18 is, thus, the second phagocyte receptor, in addition to CD14, which has been shown to have the capacity to activate cells after binding to LPS. The function of this receptor in normal phagocytes may be limited to the recognition of LPS in infected tissues, where LPS-CD14 interactions are not favored because of the absence of serum proteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hynes RO. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. [PubMed]
  • Anderson DC, Springer TA. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175–194. [PubMed]
  • Springer TA, Miller LJ, Anderson DC. p150,95, the third member of the Mac-1, LFA-1 human leukocyte adhesion glycoprotein family. J Immunol. 1986 Jan;136(1):240–245. [PubMed]
  • Sanchez-Madrid F, Nagy JA, Robbins E, Simon P, Springer TA. A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med. 1983 Dec 1;158(6):1785–1803. [PMC free article] [PubMed]
  • Lanier LL, Arnaout MA, Schwarting R, Warner NL, Ross GD. p150/95, Third member of the LFA-1/CR3 polypeptide family identified by anti-Leu M5 monoclonal antibody. Eur J Immunol. 1985 Jul;15(7):713–718. [PubMed]
  • Miller LJ, Schwarting R, Springer TA. Regulated expression of the Mac-1, LFA-1, p150,95 glycoprotein family during leukocyte differentiation. J Immunol. 1986 Nov 1;137(9):2891–2900. [PubMed]
  • Freudenthal PS, Steinman RM. The distinct surface of human blood dendritic cells, as observed after an improved isolation method. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7698–7702. [PubMed]
  • Stacker SA, Springer TA. Leukocyte integrin P150,95 (CD11c/CD18) functions as an adhesion molecule binding to a counter-receptor on stimulated endothelium. J Immunol. 1991 Jan 15;146(2):648–655. [PubMed]
  • Loike JD, Sodeik B, Cao L, Leucona S, Weitz JI, Detmers PA, Wright SD, Silverstein SC. CD11c/CD18 on neutrophils recognizes a domain at the N terminus of the A alpha chain of fibrinogen. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):1044–1048. [PubMed]
  • Postigo AA, Corbí AL, Sánchez-Madrid F, de Landázuri MO. Regulated expression and function of CD11c/CD18 integrin on human B lymphocytes. Relation between attachment to fibrinogen and triggering of proliferation through CD11c/CD18. J Exp Med. 1991 Dec 1;174(6):1313–1322. [PMC free article] [PubMed]
  • Micklem KJ, Sim RB. Isolation of complement-fragment-iC3b-binding proteins by affinity chromatography. The identification of p150,95 as an iC3b-binding protein. Biochem J. 1985 Oct 1;231(1):233–236. [PubMed]
  • Bilsland CA, Diamond MS, Springer TA. The leukocyte integrin p150,95 (CD11c/CD18) as a receptor for iC3b. Activation by a heterologous beta subunit and localization of a ligand recognition site to the I domain. J Immunol. 1994 May 1;152(9):4582–4589. [PubMed]
  • Wright SD, Jong MT. Adhesion-promoting receptors on human macrophages recognize Escherichia coli by binding to lipopolysaccharide. J Exp Med. 1986 Dec 1;164(6):1876–1888. [PMC free article] [PubMed]
  • Wright SD, Detmers PA, Aida Y, Adamowski R, Anderson DC, Chad Z, Kabbash LG, Pabst MJ. CD18-deficient cells respond to lipopolysaccharide in vitro. J Immunol. 1990 Apr 1;144(7):2566–2571. [PubMed]
  • Haziot A, Chen S, Ferrero E, Low MG, Silber R, Goyert SM. The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J Immunol. 1988 Jul 15;141(2):547–552. [PubMed]
  • Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990 Sep 21;249(4975):1431–1433. [PubMed]
  • Schumann RR, Leong SR, Flaggs GW, Gray PW, Wright SD, Mathison JC, Tobias PS, Ulevitch RJ. Structure and function of lipopolysaccharide binding protein. Science. 1990 Sep 21;249(4975):1429–1431. [PubMed]
  • Golenbock DT, Hampton RY, Qureshi N, Takayama K, Raetz CR. Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. J Biol Chem. 1991 Oct 15;266(29):19490–19498. [PubMed]
  • Kirkland TN, Qureshi N, Takayama K. Diphosphoryl lipid A derived from lipopolysaccharide (LPS) of Rhodopseudomonas sphaeroides inhibits activation of 70Z/3 cells by LPS. Infect Immun. 1991 Jan;59(1):131–136. [PMC free article] [PubMed]
  • Kovach NL, Yee E, Munford RS, Raetz CR, Harlan JM. Lipid IVA inhibits synthesis and release of tumor necrosis factor induced by lipopolysaccharide in human whole blood ex vivo. J Exp Med. 1990 Jul 1;172(1):77–84. [PMC free article] [PubMed]
  • Takayama K, Qureshi N, Beutler B, Kirkland TN. Diphosphoryl lipid A from Rhodopseudomonas sphaeroides ATCC 17023 blocks induction of cachectin in macrophages by lipopolysaccharide. Infect Immun. 1989 Apr;57(4):1336–1338. [PMC free article] [PubMed]
  • Kitchens RL, Ulevitch RJ, Munford RS. Lipopolysaccharide (LPS) partial structures inhibit responses to LPS in a human macrophage cell line without inhibiting LPS uptake by a CD14-mediated pathway. J Exp Med. 1992 Aug 1;176(2):485–494. [PMC free article] [PubMed]
  • Diamond MS, Garcia-Aguilar J, Bickford JK, Corbi AL, Springer TA. The I domain is a major recognition site on the leukocyte integrin Mac-1 (CD11b/CD18) for four distinct adhesion ligands. J Cell Biol. 1993 Feb;120(4):1031–1043. [PMC free article] [PubMed]
  • Golenbock DT, Liu Y, Millham FH, Freeman MW, Zoeller RA. Surface expression of human CD14 in Chinese hamster ovary fibroblasts imparts macrophage-like responsiveness to bacterial endotoxin. J Biol Chem. 1993 Oct 15;268(29):22055–22059. [PubMed]
  • Delude RL, Fenton MJ, Savedra R, Jr, Perera PY, Vogel SN, Thieringer R, Golenbock DT. CD14-mediated translocation of nuclear factor-kappa B induced by lipopolysaccharide does not require tyrosine kinase activity. J Biol Chem. 1994 Sep 2;269(35):22253–22260. [PubMed]
  • Libermann TA, Baltimore D. Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol Cell Biol. 1990 May;10(5):2327–2334. [PMC free article] [PubMed]
  • Shakhov AN, Collart MA, Vassalli P, Nedospasov SA, Jongeneel CV. Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages. J Exp Med. 1990 Jan 1;171(1):35–47. [PMC free article] [PubMed]
  • Shimizu H, Mitomo K, Watanabe T, Okamoto S, Yamamoto K. Involvement of a NF-kappa B-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines. Mol Cell Biol. 1990 Feb;10(2):561–568. [PMC free article] [PubMed]
  • Sanchez-Madrid F, Krensky AM, Ware CF, Robbins E, Strominger JL, Burakoff SJ, Springer TA. Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7489–7493. [PubMed]
  • Urlaub G, Mitchell PJ, Kas E, Chasin LA, Funanage VL, Myoda TT, Hamlin J. Effect of gamma rays at the dihydrofolate reductase locus: deletions and inversions. Somat Cell Mol Genet. 1986 Nov;12(6):555–566. [PubMed]
  • Diamond MS, Springer TA. A subpopulation of Mac-1 (CD11b/CD18) molecules mediates neutrophil adhesion to ICAM-1 and fibrinogen. J Cell Biol. 1993 Jan;120(2):545–556. [PMC free article] [PubMed]
  • Goldblum SE, Brann TW, Ding X, Pugin J, Tobias PS. Lipopolysaccharide (LPS)-binding protein and soluble CD14 function as accessory molecules for LPS-induced changes in endothelial barrier function, in vitro. J Clin Invest. 1994 Feb;93(2):692–702. [PMC free article] [PubMed]
  • Hailman E, Lichenstein HS, Wurfel MM, Miller DS, Johnson DA, Kelley M, Busse LA, Zukowski MM, Wright SD. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med. 1994 Jan 1;179(1):269–277. [PMC free article] [PubMed]
  • Wright SD, Ramos RA, Patel M, Miller DS. Septin: a factor in plasma that opsonizes lipopolysaccharide-bearing particles for recognition by CD14 on phagocytes. J Exp Med. 1992 Sep 1;176(3):719–727. [PMC free article] [PubMed]
  • Frey EA, Miller DS, Jahr TG, Sundan A, Bazil V, Espevik T, Finlay BB, Wright SD. Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med. 1992 Dec 1;176(6):1665–1671. [PMC free article] [PubMed]
  • Arditi M, Zhou J, Dorio R, Rong GW, Goyert SM, Kim KS. Endotoxin-mediated endothelial cell injury and activation: role of soluble CD14. Infect Immun. 1993 Aug;61(8):3149–3156. [PMC free article] [PubMed]
  • Pugin J, Schürer-Maly CC, Leturcq D, Moriarty A, Ulevitch RJ, Tobias PS. Lipopolysaccharide activation of human endothelial and epithelial cells is mediated by lipopolysaccharide-binding protein and soluble CD14. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2744–2748. [PubMed]
  • Read MA, Cordle SR, Veach RA, Carlisle CD, Hawiger J. Cell-free pool of CD14 mediates activation of transcription factor NF-kappa B by lipopolysaccharide in human endothelial cells. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9887–9891. [PubMed]
  • Haziot A, Rong GW, Silver J, Goyert SM. Recombinant soluble CD14 mediates the activation of endothelial cells by lipopolysaccharide. J Immunol. 1993 Aug 1;151(3):1500–1507. [PubMed]
  • Wright SD, Tobias PS, Ulevitch RJ, Ramos RA. Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages. J Exp Med. 1989 Oct 1;170(4):1231–1241. [PMC free article] [PubMed]
  • Fuhlbrigge RC, Chaplin DD, Kiely JM, Unanue ER. Regulation of interleukin 1 gene expression by adherence and lipopolysaccharide. J Immunol. 1987 Jun 1;138(11):3799–3802. [PubMed]
  • Couturier C, Haeffner-Cavaillon N, Weiss L, Fischer E, Kazatchkine MD. Induction of cell-associated interleukin 1 through stimulation of the adhesion-promoting proteins LFA-1 (CD11a/CD18) and CR3 (CD11b/CD18) of human monocytes. Eur J Immunol. 1990 May;20(5):999–1005. [PubMed]
  • Berton G, Laudanna C, Sorio C, Rossi F. Generation of signals activating neutrophil functions by leukocyte integrins: LFA-1 and gp150/95, but not CR3, are able to stimulate the respiratory burst of human neutrophils. J Cell Biol. 1992 Feb;116(4):1007–1017. [PMC free article] [PubMed]
  • Lacal PM, Balsinde J, Cabañas C, Bernabeu C, Sánchez-Madrid F, Mollinedo F. The CD11c antigen couples concanavalin A binding to generation of superoxide anion in human phagocytes. Biochem J. 1990 Jun 15;268(3):707–712. [PubMed]
  • Wright SD. Multiple receptors for endotoxin. Curr Opin Immunol. 1991 Feb;3(1):83–90. [PubMed]
  • Lynn WA, Liu Y, Golenbock DT. Neither CD14 nor serum is absolutely necessary for activation of mononuclear phagocytes by bacterial lipopolysaccharide. Infect Immun. 1993 Oct;61(10):4452–4461. [PMC free article] [PubMed]

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