The versatile functions of complement C3-derived ligands

Immunological Reviews

Volumn 274, Issue 1, 2016, Pages 127-140

  Erdei, Anna ^a,b   Sándor, Noémi ^b   Mácsik Valent, Bernadett ^a   Lukácsi, Szilvia ^a   Kremlitzka, Mariann ^b   Bajtay, Zsuzsa ^a  

^a EÖTVÖS LORÁND UNIVERSITY   (Hungary)

^b MTA ELTE Immunology Research Group Eötvös University   (Hungary)

Author keywords

B cell; cell activation; complement; dendritic cell; monocyte macrophage

Indexed keywords

COMPLEMENT COMPONENT C3; COMPLEMENT RECEPTOR; LIGAND; PEPTIDE;

ANTIGEN PRESENTING CELL; B LYMPHOCYTE ACTIVATION; COMPLEMENT SYSTEM; COVALENT BOND; DENDRITIC CELL; EXOSOME; HUMAN; HUMORAL IMMUNITY; IMMUNOMODULATION; LYMPHOCYTE PROLIFERATION; LYMPHOCYTE SUBPOPULATION; MACROPHAGE; MONOCYTE; PHAGOCYTOSIS; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE ACTIVATION; ANIMAL; ANIMAL MODEL; CELLULAR IMMUNITY; IMMUNOLOGY; LIVER; MOUSE; T LYMPHOCYTE;

ANIMALS; COMPLEMENT C3; HUMANS; IMMUNITY, CELLULAR; IMMUNITY, HUMORAL; IMMUNOMODULATION; LIVER; MICE; MODELS, ANIMAL; PEPTIDES; PHAGOCYTOSIS; T-LYMPHOCYTES;

EID: 84992457824     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12498     Document Type: Review

References (153)

1. Colten HR. Molecular biology of complement. BioEssays. 1986;4:249–254.
2. Erdei A, Fust G, Gergely J. The role of C3 in the immune response. Immunol Today. 1991;12:332–337.
3. Andrews PA, Zhou W, Sacks SH. Tissue synthesis of complement as an immune regulator. Mol Med Today. 1995;1:202–207.
4. Klos A, Wende E, Wareham KJ, Monk PN. International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol Rev. 2013;65:500–543.
5. Sacks SH. Complement fragments C3a and C5a: the salt and pepper of the immune response. Eur J Immunol. 2010;40:668–670.
6. Gros P, Milder FJ, Janssen BJ. Complement driven by conformational changes. Nat Rev Immunol. 2008;8:48–58.
7. Law SK, Levine RP. Interaction between the third complement protein and cell surface macromolecules. Proc Natl Acad Sci USA. 1977;74:2701–2705.
8. Helmy KY, Katschke KJ Jr, Gorgani NN, et al. CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens. Cell. 2006;124:915–927.
9. Sim RB, Twose TM, Paterson DS, Sim E. The covalent-binding reaction of complement component C3. Biochem J. 1981;193:115–127.
10. Gadjeva M, Dodds AW, Taniguchi-Sidle A, Willis AC, Isenman DE, Law SK. The covalent binding reaction of complement component C3. J Immunol. 1998;161:985–990.
11. Nelson RA Jr. The immune-adherence phenomenon; an immunologically specific reaction between microorganisms and erythrocytes leading to enhanced phagocytosis. Science. 1953;118:733–737.
12. Fearon DT. Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J Exp Med. 1980;152:20–30.
13. Bellinger-Kawahara C, Horwitz MA. Complement component C3 fixes selectively to the major outer membrane protein (MOMP) of Legionella pneumophila and mediates phagocytosis of liposome-MOMP complexes by human monocytes. J Exp Med. 1990;172:1201–1210.
14. Puentes SM, Sacks DL, da Silva RP, Joiner KA. Complement binding by two developmental stages of Leishmania major promastigotes varying in expression of a surface lipophosphoglycan. J Exp Med. 1988;167:887–902.
15. Schlesinger LS, Horwitz MA. Phenolic glycolipid-1 of Mycobacterium leprae binds complement component C3 in serum and mediates phagocytosis by human monocytes. J Exp Med. 1991;174:1031–1038.
16. Mueller-Ortiz SL, Wanger AR, Norris SJ. Mycobacterial protein HbhA binds human complement component C3. Infect Immun. 2001;69:7501–7511.
17. Karnchanaphanurach P, Mirchev R, Ghiran I, et al. C3b deposition on human erythrocytes induces the formation of a membrane skeleton-linked protein complex. J Clin Invest. 2009;119:788–801.
18. Mold C, Nemerow GR, Bradt BM, Cooper NR. CR2 is a complement activator and the covalent binding site for C3 during alternative pathway activation by Raji cells. J Immunol. 1988;140:1923–1929.
19. Praz F, Karsenty G, Binet JL, Lesavre P. Complement alternative pathway activation by chronic lymphocytic leukemia cells: its role in their hepatosplenic localization. Blood. 1984;63:463–467.
20. Marquart HV, Gronbaek K, Christensen BE, Svehag SE, Leslie RG. Complement activation by malignant B cells from patients with chronic lymphocytic leukaemia (CLL). Clin Exp Immunol. 1995;102:575–581.
21. Sissons JG, Oldstone MB, Schreiber RD. Antibody-independent activation of the alternative complement pathway by measles virus-infected cells. Proc Natl Acad Sci USA. 1980;77:559–562.
22. Ramos OF, Sarmay G, Klein E, Yefenof E, Gergely J. Complement-dependent cellular cytotoxicity: lymphoblastoid lines that activate complement component 3 (C3) and express C3 receptors have increased sensitivity to lymphocyte-mediated lysis in the presence of fresh human serum. Proc Natl Acad Sci USA. 1985;82:5470–5474.
23. Erdei A, Fust G, Gyenes J, Fabry Z, Gergely J. C3b acceptors on human peripheral blood mononuclear cells; characterization and functional role. Immunology. 1983;49:423–430.
24. Marquart HV, Svehag SE, Leslie RG. CR2 is the primary acceptor site for C3 during alternative pathway activation of complement on human peripheral B lymphocytes. J Immunol. 1994;153:307–315.
25. Maison CM, Villiers CL, Colomb MG. Secretion, cleavage and binding of complement component C3 by the human monocytic cell line U937. Biochem J. 1989;261:407–413.
26. Matsumoto M, Seya T. Homologous C3 deposition and homotypic cell adhesion in a human myeloid cell line, P39. Eur J Immunol. 1993;23:2270–2278.
27. di Renzo L, Longo A, Morgante E, et al. C3 molecules internalize and enhance the growth of Lewis lung carcinoma cells. Immunobiology. 1999;200:92–105.
28. Law SK, Dodds AW. The internal thioester and the covalent binding properties of the complement proteins C3 and C4. Protein Sci. 1997;6:263–274.
29. Erdei A, Kohler V, Schafer H, Burger R. Macrophage-bound C3 fragments as adhesion molecules modulate presentation of exogenous antigens. Immunobiology. 1992;185:314–326.
30. Olesen EH, Johnson AA, Damgaard G, Leslie RG. The requirement of localized, CR2-mediated, alternative pathway activation of complement for covalent deposition of C3 fragments on normal B cells. Immunology. 1998;93:177–183.
31. Bajtay Z, Kacani L, Erdei A, Dierich MP. HIV-1 induces human monocyte-derived macrophages to produce C3 and to fix C3 on their surface. J Leukoc Biol. 1998;63:463–468.
32. Kerekes K, Prechl J, Bajtay Z, Jozsi M, Erdei A. A further link between innate and adaptive immunity: C3 deposition on antigen-presenting cells enhances the proliferation of antigen-specific T cells. Int Immunol. 1998;10:1923–1930.
33. Kerekes K, Cooper PD, Prechl J, Jozsi M, Bajtay Z, Erdei A. Adjuvant effect of gamma-inulin is mediated by C3 fragments deposited on antigen-presenting cells. J Leukoc Biol. 2001;69:69–74.
34. Papp K, Vegh P, Prechl J, et al. B lymphocytes and macrophages release cell membrane deposited C3-fragments on exosomes with T cell response-enhancing capacity. Mol Immunol. 2008;45:2343–2351.
35. Nielsen CH, Pedersen ML, Marquart HV, Prodinger WM, Leslie RG. The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells. Eur J Immunol. 2002;32:1359–1367.
36. Sandor N, Pap D, Prechl J, Erdei A, Bajtay Z. A novel, complement-mediated way to enhance the interplay between macrophages, dendritic cells and T lymphocytes. Mol Immunol. 2009;47:438–448.
37. Erdei A, Benczur M, Fabry Z, Dierich MP, Gergely J. C3 cleaved by membrane proteases binds to C3b acceptors expressed on concanavalin A-stimulated human lymphocytes and enhances antibody-dependent cellular cytotoxicity. Scand J Immunol. 1984;20:125–131.
38. Torok K, Kremlitzka M, Sandor N, Toth EA, Bajtay Z, Erdei A. Human T cell derived, cell-bound complement iC3b is integrally involved in T cell activation. Immunol Lett. 2012;143:131–136.
39. Barro CD, Villiers CL, Colomb MG. Covalent binding of non-proteolysed C3 to Jurkat T cells. Mol Immunol. 1991;28:711–717.
40. Ghebrehiwet B, Medicus RG, Muller-Eberhard HJ. Potentiation of antiboty-dependent cell-mediated cytotoxicity by target cell-bound C3b. J Immunol. 1979;123:1285–1288.
41. Kemper C, Atkinson JP. T-cell regulation: with complements from innate immunity. Nat Rev Immunol. 2007;7:9–18.
42. Heeger PS, Kemper C. Novel roles of complement in T effector cell regulation. Immunobiology. 2012;217:216–224.
43. Zhou W, Peng Q, Li K, Sacks SH. Role of dendritic cell synthesis of complement in the allospecific T cell response. Mol Immunol. 2007;44:57–63.
44. van der Touw W, Cravedi P, Kwan WH, Paz-Artal E, Merad M, Heeger PS. Cutting edge: receptors for C3a and C5a modulate stability of alloantigen-reactive induced regulatory T cells. J Immunol. 2013;190:5921–5925.
45. Raposo G, Nijman HW, Stoorvogel W, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183:1161–1172.
46. Reis ES, Barbuto JA, Isaac L. Complement components, regulators and receptors are produced by human monocyte-derived dendritic cells. Immunobiology. 2007;212:151–157.
47. van Kooten C, Fiore N, Trouw LA, et al. Complement production and regulation by dendritic cells: molecular switches between tolerance and immunity. Mol Immunol. 2008;45:4064–4072.
48. Zhou W, Patel H, Li K, Peng Q, Villiers MB, Sacks SH. Macrophages from C3-deficient mice have impaired potency to stimulate alloreactive T cells. Blood. 2006;107:2461–2469.
49. Ghannam A, Pernollet M, Fauquert JL, et al. Human C3 deficiency associated with impairments in dendritic cell differentiation, memory B cells, and regulatory T cells. J Immunol. 2008;181:5158–5166.
50. Ehirchiou D, Xiong Y, Xu G, Chen W, Shi Y, Zhang L. CD11b facilitates the development of peripheral tolerance by suppressing Th17 differentiation. J Exp Med. 2007;204:1519–1524.
51. Schmidt J, Klempp C, Buchler MW, Marten A. Release of iC3b from apoptotic tumor cells induces tolerance by binding to immature dendritic cells in vitro and in vivo. Cancer Immunol Immunother. 2006;55:31–38.
52. Skoberne M, Somersan S, Almodovar W, et al. The apoptotic-cell receptor CR3, but not alphavbeta5, is a regulator of human dendritic-cell immunostimulatory function. Blood. 2006;108:947–955.
53. Sohn JH, Bora PS, Suk HJ, Molina H, Kaplan HJ, Bora NS. Tolerance is dependent on complement C3 fragment iC3b binding to antigen-presenting cells. Nat Med. 2003;9:206–212.
54. Ezekowitz RA, Sim RB, Hill M, Gordon S. Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan. J Exp Med. 1984;159:244–260.
55. Baudino L, Sardini A, Ruseva MM, et al. C3 opsonization regulates endocytic handling of apoptotic cells resulting in enhanced T-cell responses to cargo-derived antigens. Proc Natl Acad Sci USA. 2014;111:1503–1508.
56. + T cells. Immunity. 2008;28:425–435.
57. Cravedi P, Leventhal J, Lakhani P, Ward SC, Donovan MJ, Heeger PS. Immune cell-derived C3a and C5a costimulate human T cell alloimmunity. Am J Transplant. 2013;13:2530–2539.
58. Li K, Anderson KJ, Peng Q, et al. Cyclic AMP plays a critical role in C3a-receptor-mediated regulation of dendritic cells in antigen uptake and T-cell stimulation. Blood. 2008;112:5084–5094.
59. Pantazis P, Kalyanaraman VS, Bing DH. Synthesis of the third component of complement (C3) by lectin-activated and HTLV-infected human T-cells. Mol Immunol. 1990;27:283–289.
60. Cardone J, Le Friec G, Vantourout P, et al. Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells. Nat Immunol. 2010;11:862–871.
61. Kurtz CB, O'Toole E, Christensen SM, Weis JH. The murine complement receptor gene family. IV. Alternative splicing of Cr2 gene transcripts predicts two distinct gene products that share homologous domains with both human CR2 and CR1. J Immunol. 1990;144:3581–3591.
62. Jacobson AC, Weis JH. Comparative functional evolution of human and mouse CR1 and CR2. J Immunol. 2008;181:2953–2959.
63. Holers VM. Complement and its receptors: new insights into human disease. Annu Rev Immunol. 2014;32:433–459.
64. Carroll MC. The role of complement and complement receptors in induction and regulation of immunity. Annu Rev Immunol. 1998;16:545–568.
65. Sim RB, Malhotra V, Day AJ, Erdei A. Structure and specificity of complement receptors. Immunol Lett. 1987;14:183–190.
66. Ogembo JG, Kannan L, Ghiran I, et al. Human complement receptor type 1/CD35 is an Epstein-Barr Virus receptor. Cell Rep. 2013;3:371–385.
67. Wagner C, Ochmann C, Schoels M, et al. The complement receptor 1, CR1 (CD35), mediates inhibitory signals in human T-lymphocytes. Mol Immunol. 2006;43:643–651.
68. + T cells contributes to generation of regulatory T cells. Immunol Lett. 2015;164:117–124.
69. Jozsi M, Prechl J, Bajtay Z, Erdei A. Complement receptor type 1 (CD35) mediates inhibitory signals in human B lymphocytes. J Immunol. 2002;168:2782–2788.
70. Kremlitzka M, Polgar A, Fulop L, Kiss E, Poor G, Erdei A. Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell functions in rheumatoid arthritis patients. Int Immunol. 2013;25:25–33.
71. Watry D, Hedrick JA, Siervo S, et al. Infection of human thymocytes by Epstein-Barr virus. J Exp Med. 1991;173:971–980.
72. Tuveson DA, Ahearn JM, Matsumoto AK, Fearon DT. Molecular interactions of complement receptors on B lymphocytes: a CR1/CR2 complex distinct from the CR2/CD19 complex. J Exp Med. 1991;173:1083–1089.
73. Carter RH, Fearon DT. CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science. 1992;256:105–107.
74. Tsokos GC, Thyphronitis G, Jack RM, Finkelman FD. Ligand-loaded but not free complement receptors for C3b/C4b and C3d co-cap with cross-linked B cell surface IgM and IgD. J Immunol. 1988;141:1261–1266.
75. Carter RH, Fearon DT. Polymeric C3dg primes human B lymphocytes for proliferation induced by anti-IgM. J Immunol. 1989;143:1755–1760.
76. Fingeroth JD, Weis JJ, Tedder TF, Strominger JL, Biro PA, Fearon DT. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci USA. 1984;81:4510–4514.
77. Aubry JP, Pochon S, Graber P, Jansen KU, Bonnefoy JY. CD21 is a ligand for CD23 and regulates IgE production. Nature. 1992;358:505–507.
78. Pepys MB. Role of complement in induction of antibody production in vivo. Effect of cobra factor and other C3-reactive agents on thymus-dependent and thymus-independent antibody responses. J Exp Med. 1974;140:126–145.
79. Ahearn JM, Fischer MB, Croix D, et al. Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen. Immunity. 1996;4:251–262.
80. Molina H, Holers VM, Li B, et al. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. Proc Natl Acad Sci USA. 1996;93:3357–3361.
81. Dempsey PW, Allison ME, Akkaraju S, Goodnow CC, Fearon DT. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science. 1996;271:348–350.
82. Melchers F, Erdei A, Schulz T, Dierich MP. Growth control of activated, synchronized murine B cells by the C3d fragment of human complement. Nature. 1985;317:264–267.
83. Erdei A, Melchers F, Schulz T, Dierich M. The action of human C3 in soluble or cross-linked form with resting and activated murine B lymphocytes. Eur J Immunol. 1985;15:184–188.
84. Prechl J, Tchorbanov A, Horvath A, et al. Targeting of influenza epitopes to murine CR1/CR2 using single-chain antibodies. Immunopharmacology. 1999;42:159–165.
85. Baiu DC, Prechl J, Tchorbanov A, et al. Modulation of the humoral immune response by antibody-mediated antigen targeting to complement receptors and Fc receptors. J Immunol. 1999;162:3125–3130.
86. Arvieux J, Yssel H, Colomb MG. Antigen-bound C3b and C4b enhance antigen-presenting cell function in activation of human T-cell clones. Immunology. 1988;65:229–235.
87. Villiers MB, Villiers CL, Laharie AM, Marche PN. Amplification of the antibody response by C3b complexed to antigen through an ester link. J Immunol. 1999;162:3647–3652.
88. Prechl J, Erdei A. Immunomodulatory functions of murine CR1/2. Immunopharmacology. 2000;49:117–124.
89. Carroll MC. Complement and humoral immunity. Vaccine. 2008;26(Suppl 8):I28–33.
90. Carroll MC, Isenman DE. Regulation of humoral immunity by complement. Immunity. 2012;37:199–207.
91. Bohnsack JF, Cooper NR. CR2 ligands modulate human B cell activation. J Immunol. 1988;141:2569–2576.
92. Kuraya M, Nilsson B, Nilsson-Ekdahl K, Klein E. C3d-mediated negative and positive signals on the proliferation of human B cells separated from blood. Immunol Lett. 1990;26:51–58.
93. Tsokos GC, Lambris JD, Finkelman FD, Anastassiou ED, June CH. Monovalent ligands of complement receptor 2 inhibit whereas polyvalent ligands enhance anti-Ig-induced human B cell intracytoplasmic free calcium concentration. J Immunol. 1990;144:1640–1645.
94. Nemerow GR, McNaughton ME, Cooper NR. Binding of monoclonal antibody to the Epstein Barr virus (EBV)/CR2 receptor induces activation and differentiation of human B lymphocytes. J Immunol. 1985;135:3068–3073.
95. Frade R, Crevon MC, Barel M, et al. Enhancement of human B cell proliferation by an antibody to the C3d receptor, the gp 140 molecule. Eur J Immunol. 1985;15:73–76.
96. Luxembourg AT, Cooper NR. Modulation of signaling via the B cell antigen receptor by CD21, the receptor for C3dg and EBV. J Immunol. 1994;153:4448–4457.
97. Daha MR, Bloem AC, Ballieux RE. Immunoglobulin production by human peripheral lymphocytes induced by anti-C3 receptor antibodies. J Immunol. 1984;132:1197–1201.
98. Weiss L, Delfraissy JF, Vazquez A, Wallon C, Galanaud P, Kazatchkine MD. Monoclonal antibodies to the human C3b/C4b receptor (CR1) enhance specific B cell differentiation. J Immunol. 1987;138:2988–2993.
99. Tedder TF, Weis JJ, Clement LT, Fearon DT, Cooper MD. The role of receptors for complement in the induction of polyclonal B-cell proliferation and differentiation. J Clin Immunol. 1986;6:65–73.
100. Berger M, Fleisher TA. Native C3 does not bind to the C3b receptor (CR1) of human blood B lymphocytes or alter immunoglobulin synthesis. J Immunol. 1983;130:1021–1023.
101. Tsokos GC, Berger M, Balow JE. Modulation of human B cell immunoglobulin secretion by the C3b component of complement. J Immunol. 1984;132:622–626.
102. Kerekov NS, Mihaylova NM, Grozdev I, et al. Elimination of autoreactive B cells in humanized SCID mouse model of SLE. Eur J Immunol. 2011;41:3301–3311.
103. Iida K, Mornaghi R, Nussenzweig V. Complement receptor (CR1) deficiency in erythrocytes from patients with systemic lupus erythematosus. J Exp Med. 1982;155:1427–1438.
104. Wilson JG, Ratnoff WD, Schur PH, Fearon DT. Decreased expression of the C3b/C4b receptor (CR1) and the C3d receptor (CR2) on B lymphocytes and of CR1 on neutrophils of patients with systemic lupus erythematosus. Arthritis Rheum. 1986;29:739–747.
105. Illges H, Braun M, Peter HH, Melchers I. Reduced expression of the complement receptor type 2 (CR2, CD21) by synovial fluid B and T lymphocytes. Clin Exp Immunol. 2000;122:270–276.
106. Isaak A, Gergely P Jr, Szekeres Z, et al. Physiological up-regulation of inhibitory receptors Fc gamma RII and CR1 on memory B cells is lacking in SLE patients. Int Immunol. 2008;20:185–192.
107. Mitchell JP, Enyedy EJ, Nambiar MP, Lees A, Tsokos GC. Engagement of complement receptor 2 on the surface of B cells from patients with systemic lupus erythematosus contributes to the increased responsiveness to antigen stimulation. Lupus. 2002;11:299–303.
108. Prodeus AP, Goerg S, Shen LM, et al. A critical role for complement in maintenance of self-tolerance. Immunity. 1998;9:721–731.
109. Wehr C, Eibel H, Masilamani M, et al. A new CD21low B cell population in the peripheral blood of patients with SLE. Clin Immunol. 2004;113:161–171.
110. Tan SM. The leucocyte beta2 (CD18) integrins: the structure, functional regulation and signalling properties. Biosci Rep. 2012;32:241–269.
111. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110:673–687.
112. Corbi AL, Kishimoto TK, Miller LJ, Springer TA. The human leukocyte adhesion glycoprotein Mac-1 (complement receptor type 3, CD11b) alpha subunit. Cloning, primary structure, and relation to the integrins, von Willebrand factor and factor B. J Biol Chem. 1988;263:12403–12411.
113. Ross GD, Reed W, Dalzell JG, Becker SE, Hogg N. Macrophage cytoskeleton association with CR3 and CR4 regulates receptor mobility and phagocytosis of iC3b-opsonized erythrocytes. J Leukoc Biol. 1992;51:109–117.
114. Miller LJ, Wiebe M, Springer TA. Purification and alpha subunit N-terminal sequences of human Mac-1 and p150,95 leukocyte adhesion proteins. J Immunol. 1987;138:2381–2383.
115. Altieri DC, Agbanyo FR, Plescia J, Ginsberg MH, Edgington TS, Plow EF. A unique recognition site mediates the interaction of fibrinogen with the leukocyte integrin Mac-1 (CD11b/CD18). J Biol Chem. 1990;265:12119–12122.
116. Diamond MS, Staunton DE, de Fougerolles AR, et al. ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). J Cell Biol. 1990;111:3129–3139.
117. Van Strijp JA, Russell DG, Tuomanen E, Brown EJ, Wright SD. Ligand specificity of purified complement receptor type three (CD11b/CD18, alpha m beta 2, Mac-1). Indirect effects of an Arg-Gly-Asp (RGD) sequence. J Immunol. 1993;151:3324–3336.
118. Ueda T, Rieu P, Brayer J, Arnaout MA. Identification of the complement iC3b binding site in the beta 2 integrin CR3 (CD11b/CD18). Proc Natl Acad Sci USA. 1994;91:10680–10684.
119. Liddington RC, Ginsberg MH. Integrin activation takes shape. J Cell Biol. 2002;158:833–839.
120. Gupta V, Gylling A, Alonso JL, et al. The beta-tail domain (betaTD) regulates physiologic ligand binding to integrin CD11b/CD18. Blood. 2007;109:3513–3520.
121. Li Y, Zhang L. The fourth blade within the beta-propeller is involved specifically in C3bi recognition by integrin alpha M beta 2. J Biol Chem. 2003;278:34395–34402.
122. Chen X, Xie C, Nishida N, Li Z, Walz T, Springer TA. Requirement of open headpiece conformation for activation of leukocyte integrin alphaXbeta2. Proc Natl Acad Sci USA. 2010;107:14727–14732.
123. Chen X, Yu Y, Mi LZ, Walz T, Springer TA. Molecular basis for complement recognition by integrin alphaXbeta2. Proc Natl Acad Sci USA. 2012;109:4586–4591.
124. Zhang L, Plow EF. Overlapping, but not identical, sites are involved in the recognition of C3bi, neutrophil inhibitory factor, and adhesive ligands by the alphaMbeta2 integrin. J Biol Chem. 1996;271:18211–18216.
125. Yan J, Vetvicka V, Xia Y, et al. Beta-glucan, a “specific” biologic response modifier that uses antibodies to target tumors for cytotoxic recognition by leukocyte complement receptor type 3 (CD11b/CD18). J Immunol. 1999;163:3045–3052.
126. Oliva CR, Swiecki MK, Griguer CE, et al. The integrin Mac-1 (CR3) mediates internalization and directs Bacillus anthracis spores into professional phagocytes. Proc Natl Acad Sci USA. 2008;105:1261–1266.
127. Peyron P, Bordier C, N'Diaye EN, Maridonneau-Parini I. Nonopsonic phagocytosis of Mycobacterium kansasii by human neutrophils depends on cholesterol and is mediated by CR3 associated with glycosylphosphatidylinositol-anchored proteins. J Immunol. 2000;165:5186–5191.
128. Wright SD, Levin SM, Jong MT, Chad Z, Kabbash LG. CR3 (CD11b/CD18) expresses one binding site for Arg-Gly-Asp-containing peptides and a second site for bacterial lipopolysaccharide. J Exp Med. 1989;169:175–183.
129. Ingalls RR, Golenbock DT. CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. J Exp Med. 1995;181:1473–1479.
130. Zaffran Y, Zhang L, Ellner JJ. Role of CR4 in Mycobacterium tuberculosis-human macrophages binding and signal transduction in the absence of serum. Infect Immun. 1998;66:4541–4544.
131. Prieto J, Eklund A, Patarroyo M. Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages. Cell Immunol. 1994;156:191–211.
132. Beyer M, Wang H, Peters N, et al. The beta2 integrin CD11c distinguishes a subset of cytotoxic pulmonary T cells with potent antiviral effects in vitro and in vivo. Respir Res. 2005;6:70.
133. Postigo AA, Corbi AL, Sanchez-Madrid F, de Landazuri 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;174:1313–1322.
134. Miller LJ, Bainton DF, Borregaard N, Springer TA. Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface. J Clin Invest. 1987;80:535–544.
135. Bretscher MS. Circulating integrins: alpha 5 beta 1, alpha 6 beta 4 and Mac-1, but not alpha 3 beta 1, alpha 4 beta 1 or LFA-1. EMBO J. 1992;11:405–410.
136. Le Cabec V, Carreno S, Moisand A, Bordier C, Maridonneau-Parini I. Complement receptor 3 (CD11b/CD18) mediates type I and type II phagocytosis during nonopsonic and opsonic phagocytosis, respectively. J Immunol. 2002;169:2003–2009.
137. Patel PC, Harrison RE. Membrane ruffles capture C3bi-opsonized particles in activated macrophages. Mol Biol Cell. 2008;19:4628–4639.
138. Bajtay Z, Speth C, Erdei A, Dierich MP. Cutting edge: productive HIV-1 infection of dendritic cells via complement receptor type 3 (CR3, CD11b/CD18). J Immunol. 2004;173:4775–4778.
139. Morelli AE, Larregina AT, Shufesky WJ, et al. Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production. Blood. 2003;101:611–620.
140. Verbovetski I, Bychkov H, Trahtemberg U, et al. Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and up-regulates CC chemokine receptor 7. J Exp Med. 2002;196:1553–1561.
141. Georgakopoulos T, Moss ST, Kanagasundaram V. Integrin CD11c contributes to monocyte adhesion with CD11b in a differential manner and requires Src family kinase activity. Mol Immunol. 2008;45:3671–3681.
142. Pliyev BK, Arefieva TI, Menshikov MY. Urokinase receptor (uPAR) regulates complement receptor 3 (CR3)-mediated neutrophil phagocytosis. Biochem Biophys Res Commun. 2010;397:277–282.
143. Castro FV, Tutt AL, White AL, et al. CD11c provides an effective immunotarget for the generation of both CD4 and CD8 T cell responses. Eur J Immunol. 2008;38:2263–2273.
144. White AL, Tutt AL, James S, et al. Ligation of CD11c during vaccination promotes germinal centre induction and robust humoral responses without adjuvant. Immunology. 2010;131:141–151.
145. Han S, Kim-Howard X, Deshmukh H, et al. Evaluation of imputation-based association in and around the integrin-alpha-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE). Hum Mol Genet. 2009;18:1171–1180.
146. Rubtsov AV, Rubtsova K, Fischer A, et al. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c(+) B-cell population is important for the development of autoimmunity. Blood. 2011;118:1305–1315.
147. Nicolaou F, Teodoridis JM, Park H, et al. CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras and junD. Blood. 2003;101:4033–4041.
148. Sandor N, Kristof K, Parej K, Pap D, Erdei A, Bajtay Z. CR3 is the dominant phagocytotic complement receptor on human dendritic cells. Immunobiology. 2013;218:652–663.
149. Lu H, Smith CW, Perrard J, et al. LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice. J Clin Invest. 1997;99:1340–1350.
150. Flick MJ, Du X, Witte DP, et al. Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo. J Clin Invest. 2004;113:1596–1606.
151. Ugarova TP, Yakubenko VP. Recognition of fibrinogen by leukocyte integrins. Ann N Y Acad Sci. 2001;936:368–385.
152. Singh-Jasuja H, Thiolat A, Ribon M, et al. The mouse dendritic cell marker CD11c is down-regulated upon cell activation through Toll-like receptor triggering. Immunobiology. 2013;218:28–39.
153. Thacker RI, Retzinger GS. Adsorbed fibrinogen regulates the behavior of human dendritic cells in a CD18-dependent manner. Exp Mol Pathol. 2008;84:122–130.