The complement system comprises a strong defense against various pathogens and is a major component of our innate immune system. While earlier studies have established a crucial role of complement in recognition, opsonization and enhanced phagocytosis of microorganisms by professional phagocytes such as polymorphonuclear leukocytes and macrophages, recent studies delineate an additional role of complement in initiation and maintenance of the acquired immune response. In addition, it seems that opsonization of apoptotic cells by complement may lead to polarization of the response of professional antigen-presenting cells to a more inflammatory or tolerogenic response. The present review summarizes these different contributions of complement to the shaping of the immune balance.

Keywords:
Complement, Apoptosis, Autoimmunity, Receptors, Dendritic cells
1.
Janeway CA Jr, Medzhitov R: Innate immune recognition. Annu Rev Immunol 2002;20:197–216.
2.
Gordon S: Pattern recognition receptors: Doubling up for the innate immune response. Cell 2002;111:927–930.
3.
Cooper NR, Jensen FC, Welsh RM Jr, Oldstone MB: Lysis of RNA tumor viruses by human serum: Direct antibody-independent triggering of the classical complement pathway. J Exp Med 1976;144:970–984.
4.
Alberti S, Marques G, Camprubi S, Merino S, Tomas JM, Vivanco F, Benedi VJ: C1q binding and activation of the complement classical pathway by Klebsiella pneumoniae outer membrane proteins. Infect Immun 1993;61:852–860.
5.
Jiang H, Cooper B, Robey FA, Gewurz H: DNA binds and activates complement via residues 14–26 of the human C1q A chain. J Biol Chem 1992;267:25597–25601.
6.
Jiang HX, Siegel JN, Gewurz H: Binding and complement activation by C-reactive protein via the collagen-like region of C1q and inhibition of these reactions by monoclonal antibodies to C-reactive protein and C1q. J Immunol 1991;146:2324–2330.
7.
Petersen SV, Thiel S, Jensenius JC: The mannan-binding lectin pathway of complement activation: Biology and disease association. Mol Immunol 2001;38:133–149.
8.
Pangburn MK, Schreiber RD, Muller-Eberhard HJ: C3b deposition during activation of the alternative complement pathway and the effect of deposition on the activating surface. J Immunol 1983;131:1930–1935.
9.
Liszewski MK, Farries TC, Lublin DM, Rooney IA, Atkinson JP: Control of the complement system. Adv Immunol 1996;61:201–283.
10.
Welch TR: Complement in glomerulonephritis. Nat Genet 2002;31:333–334.
11.
Vakeva AP, Agah A, Rollins SA, Matis LA, Li L, Stahl GL: Myocardial infarction and apoptosis after myocardial ischemia and reperfusion: Role of the terminal complement components and inhibition by anti-C5 therapy. Circulation 1998;97:2259–2267.
12.
Linton SM, Morgan BP: Complement activation and inhibition in experimental models of arthritis. Mol Immunol 1999;36:905–914.
13.
Shin HS, Snyderman R, Friedman E, Mellors A, Mayer MM: Chemotactic and anaphylatoxic fragment cleaved from the fifth component of guinea pig complement. Science 1968;162:361–363.
14.
Fernandez HN, Henson PM, Otani A, Hugli TE: Chemotactic response to human C3a and C5a anaphylatoxins. I. Evaluation of C3a and C5a leukotaxis in vitro and under stimulated in vivo conditions. J Immunol 1978;120:109–115.
15.
Barrington R, Zhang M, Fischer M, Carroll MC: The role of complement in inflammation and adaptive immunity. Immunol Rev 2001;180:5–15.
16.
Sjoholm AG, Berglund K, Johnson U, Laurell AB, Sturfelt G: C1 activation, with C1q in excess of functional C1 in synovial fluid from patients with rheumatoid arthritis. Int Arch Allergy Appl Immunol 1986;79:113–119.
17.
Sim RB, Moestrup SK, Stuart GR, Lynch NJ, Lu J, Schwaeble WJ, Malhotra R: Interaction of C1q and the collectins with the potential receptors calreticulin (cC1qR/collectin receptor) and megalin. Immunobiology 1998;199:208–224.
18.
Gagnon E, Duclos S, Rondeau C, Chevet E, Cameron PH, Steele-Mortimer O, Paiement J, Bergeron JJ, Desjardins M: Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages. Cell 2002;110:119–131.
19.
Ogden CA, deCathelineau A, Hoffmann PR, Bratton D, Ghebrehiwet B, Fadok VA, Henson PM: C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med 2001;194:781–795.
20.
Vandivier RW, Ogden CA, Fadok VA, Hoffmann PR, Brown KK, Botto M, Walport MJ, Fisher JH, Henson PM, Greene KE: Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: Calreticulin and CD91 as a common collectin receptor complex. J Immunol 2002;169:3978–3986.
21.
Nepomuceno RR, Henschen-Edman AH, Burgess WH, Tenner AJ: cDNA cloning and primary structure analysis of C1qR(P), the human C1q/MBL/SPA receptor that mediates enhanced phagocytosis in vitro. Immunity 1997;6:119–129.
22.
McGreal EP, Ikewaki N, Akatsu H, Morgan BP, Gasque P: Human C1qRp is identical with CD93 and the mNI-11 antigen but does not bind C1q. J Immunol 2002;168:5222–5232.
23.
Ruiz S, Henschen-Edman AH, Tenner AJ: Localization of the site on the complement component C1q required for the stimulation of neutrophil superoxide production. J Biol Chem 1995;270:30627–30634.
24.
Klickstein LB, Barbashov SF, Liu T, Jack RM, Nicholson-Weller A: Complement receptor type 1 (CR1, CD35) is a receptor for C1q. Immunity 1997;7:345–355.
25.
Ghebrehiwet B, Lim BL, Peerschke EI, Willis AC, Reid KB: Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular ‘heads’ of C1q. J Exp Med 1994;179:1809–1821.
26.
van den Berg RH, Prins F, Faber-Krol MC, Lynch NJ, Schwaeble W, Van Es LA, Daha MR: Intracellular localization of the human receptor for the globular domains of C1q. J Immunol 1997;158:3909–3916.
27.
Lynch NJ, Reid KB, van den Berg RH, Daha MR, Leigh LA, Ghebrehiwet B, Lim WB, Schwaeble WJ: Characterisation of the rat and mouse homologues of gC1qBP, a 33 kDa glycoprotein that binds to the globular ‘heads’ of C1q. FEBS Lett 1997;418:111–114.
28.
Daha MR, Klar N, Hoekzema R, Van Es LA: Enhanced Ig production by human peripheral lymphocytes induced by aggregated C1q. J Immunol 1990;144:1227–1232.
29.
van den Berg, RH, Faber-Krol, MC, Sim, RB, Daha, MR, The first subcomponent of complement, C1q, triggers the production of IL-8, IL-6, and monocyte chemoattractant peptide-1 by human umbilical vein endothelial cells. J Immunol 1998;161:6924–6930.
30.
Walport MJ, Davies KA, Botto M: C1q and systemic lupus erythematosus. Immunobiol 1998;199:265–285.
31.
Botto M, Dell’Agnola C, Bygrave AE, Thompson EM, Cook HT, Petry F, Loos M, Pandolfi PP, Walport MJ: Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 1998;19:56–59.
32.
Korb LC, Ahearn, JM: C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: Complement deficiency and systemic lupus erythematosus revisited. J Immunol 1997;158:4525–4528.
33.
Nauta AJ, Trouw LA, Daha MR, Tijsma O, Nieuwland R, Schwaeble WJ, Gingras AR, Mantovani A, Hack CE, Roos A: Direct binding of C1q to apoptotic cells and cell blebs induces complement activation. Eur J Immunol 2002;32:1726–1736.
34.
Navratil JS, Watkins SC, Wisnieski JJ, Ahearn JM: The globular heads of C1q specifically recognize surface blebs of apoptotic vascular endothelial cells. J Immunol 2001;166:3231–3239.
35.
Warren J, Mastroeni P, Dougan G, Noursadeghi M, Cohen J, Walport MJ, Botto M: Increased susceptibility of C1q-deficient mice to Salmonella enterica serovar typhimurium infection. Infect Immun 2002. 70:551–557.
36.
Butko P, Nicholson-Weller A, Wessels MR: Role of complement component C1q in the IgG-independent opsonophagocytosis of group B streptococcus. J Immunol 1999;163:2761–2768.
37.
Marschang P, Kruger U, Ochsenbauer C, Gurtler L, Hittmair A, Bosch V, Patsch JR, Dierich MP: Complement activation by HIV-1-infected cells: the role of transmembrane glycoprotein gp41. J Acquir Immune Defic Syndr Hum Retrovirol 1997;14:102–109.
38.
Jiang H, Burdick D, Glabe CG, Cotman CW, Tenner AJ: Beta-amyloid activates complement by binding to a specific region of the collagen-like domain of the C1q A chain. J Immunol 1994;152:5050–5059.
39.
Klein MA, Kaeser PS, Schwarz P, Weyd H, Xenarios I, Zinkernagel RM, Carroll MC, Verbeek JS, Botto M, Walport MJ, Molina H, Kalinke U, Acha-Orbea H, Aguzzi A: Complement facilitates early prion pathogenesis. Nat Med 2001;7:488–492.
40.
Matsushita M, Fujita T: Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. J Exp Med 1992;176:1497–1502.
41.
Thiel S, Vorup-Jensen T, Stover CM, Schwaeble W, Laursen SB, Poulsen K, Willis AC, Eggleton P, Hansen S, Holmskov U, Reid KB, Jensenius JC: A second serine protease associated with mannan-binding lectin that activates complement. Nature 1997;386:506–510.
42.
Dahl MR, Thiel S, Matsushita M, Fujita T, Willis AC, Christensen T, Vorup-Jensen T, Jensenius JC: MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 2001;15:127–135.
43.
Takahashi M, Endo Y, Fujita T, Matsushita M: A truncated form of mannose-binding lectin-associated serine protease (MASP)-2 expressed by alternative polyadenylation is a component of the lectin complement pathway. Int Immunol 1999;11:859–863.
44.
Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T: Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol 2000;165:2637–2642.
45.
Vorup-Jensen T, Petersen SV, Hansen AG, Poulsen K, Schwaeble W, Sim RB, Reid KB, Davis SJ, Thiel S, Jensenius JC: Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2. J Immunol 2000;165:2093–2100.
46.
Rossi V, Cseh S, Bally I, Thielens NM, Jensenius JC, Arlaud GJ: Substrate specificities of recombinant mannan-binding lectin-associated serine proteases-1 and -2. J Biol Chem 2001;276:40880–40887.
47.
Jack DL, Klein NJ, Turner MW: Mannose-binding lectin: Targeting the microbial world for complement attack and opsonophagocytosis. Immunol Rev 2001;180:86–99.
48.
Malhotra R, Thiel S, Reid KB, Sim RB: Human leukocyte C1q receptor binds other soluble proteins with collagen domains. J Exp Med 1990;172:955–959.
49.
Ghiran I, Barbashov SF, Klickstein LB, Tas SW, Jensenius JC, Nicholson-Weller A: Complement receptor 1/CD35 is a receptor for mannan-binding lectin. J Exp Med 2000;192:1797–1808.
50.
Garred P, Madsen HO, Svejgaard A: Genetics of human mannan-binding protein. Collect 2003;139–164.
51.
Summerfield JA, Ryder S, Sumiya M, Thursz M, Gorchein A, Monteil MA, Turner MW: Mannose binding protein gene mutations associated with unusual and severe infections in adults. Lancet 1995;345:886–889.
52.
Hibberd ML, Sumiya M, Summerfield JA, Booy R, Levin M: Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group. Lancet 1999;353:1049–1053.
53.
Graudal NA, Madsen HO, Tarp U, Svejgaard A, Jurik G, Graudal HK, Garred P: The association of variant mannose-binding lectin genotypes with radiographic outcome in rheumatoid arthritis. Arthritis Rheum 2000;43:515–521.
54.
Garred P, Pressler T, Madsen HO, Frederiksen B, Svejgaard A, Hoiby N, Schwartz M, Koch C: Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis. J Clin Invest 1999;104:431–437.
55.
Garred P, Madsen HO, Halberg P, Petersen J, Kronborg G, Svejgaard A, Andersen V, Jacobsen S: Mannose-binding lectin polymorphisms and susceptibility to infection in systemic lupus erythematosus. Arthritis Rheum 1999;42:2145–2152.
56.
Reid KB: Functional roles of the lung surfactant proteins SP-A and SP-D in innate immunity. Immunobiology 1998;199:200–207.
57.
Watford WT, Ghio AJ, Wright JR: Complement-mediated host defense in the lung. Am J Physiol Lung Cell Mol Physiol 2000;279:L790–L798.
58.
LeVine AM, Whitsett JA, Gwozdz JA, Richardson TR, Fisher JH, Burhans MS, Korfhagen TR: Distinct effects of surfactant protein A or D deficiency during bacterial infection on the lung. J Immunol 2000;165:3934–3940.
59.
LeVine AM, Gwozdz J, Stark J, Bruno M, Whitsett J, Korfhagen T: Surfactant protein-A enhances respiratory syncytial virus clearance in vivo. J Clin Invest 1999;103:1015–1021.
60.
Watford WT, Wright JR, Hester CG, Jiang H, Frank MM: Surfactant protein A regulates complement activation. J Immunol 2001;167:6593–6600.
61.
Watford WT, Smithers MB, Frank MM, Wright JR: Surfactant protein A enhances the phagocytosis of C1q-coated particles by alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 2002;283:L1011–L1022.
62.
Lu J, Le Y: Ficolins and the fibrinogen-like domain. Immunobiology 1998;199:190–199.
63.
Sugimoto R, Yae Y, Akaiwa M, Kitajima S, Shibata Y, Sato H, Hirata J, Okochi K, Izuhara K, Hamasaki N: Cloning and characterization of the Hakata antigen, a member of the ficolin/opsonin p35 lectin family. J Biol Chem 1998;273:20721–20727.
64.
Matsushita M, Endo Y, Taira S, Sato Y, Fujita T, Ichikawa N, Nakata M, Mizuochi T: A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin. J Biol Chem 1996;271:2448–2454.
65.
Teh C, Le Y, Lee SH, Lu J: M-ficolin is expressed on monocytes and is a lectin binding to N-acetyl-D-glucosamine and mediates monocyte adhesion and phagocytosis of Escherichia coli. Immunology 2000;101:225–232.
66.
Matsushita M, Kuraya M, Hamasaki N, Tsujimura M, Shiraki H, Fujita T: Activation of the lectin complement pathway by H-ficolin (Hakata antigen). J Immunol 2002;168:3502–3506.
67.
Matsushita M, Endo Y, Fujita T: Cutting edge: Complement-activating complex of ficolin and mannose-binding lectin-associated serine protease. J Immunol 2000;164:2281–2284.
68.
Nielsen CH, Fischer EM, Leslie RG: The role of complement in the acquired immune response. Immunology 2000;100:4–12.
69.
Takizawa F, Tsuji S, Nagasawa S: Enhancement of macrophage phagocytosis upon iC3b deposition on apoptotic cells. FEBS Lett 1996:397:269–272.
70.
Verbovetski I, Bychkov H, Trahtemberg U, Shapira I, Hareuveni M, Ben Tal O, Kutikov I, Gill O, Mevorach D: 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.
71.
Papadimitriou JC, Drachenberg CB, Shin ML, Trump BF: Ultrastructural studies of complement mediated cell death: a biological reaction model to plasma membrane injury. Virchows Arch 1994;424:677–685.
72.
Morgan BP: Regulation of the complement membrane attack pathway. Crit Rev Immunol 1999;19:73–198.
73.
Hila S, Soane L, Koski CL: Sublytic C5b-9-stimulated Schwann cell survival through PI 3-kinase-mediated phosphorylation of BAD. Glia 2001;36:58–67.
74.
Soane L, Rus H, Niculescu F, Shin ML: Inhibition of oligodendrocyte apoptosis by sublytic C5b-9 is associated with enhanced synthesis of bcl-2 and mediated by inhibition of caspase-3 activation. J Immunol 1999;163:6132–6138.
75.
Reiter Y, Ciobotariu A, Fishelson Z: Sublytic complement attack protects tumor cells from lytic doses of antibody and complement. Eur J Immunol 1992;22:1207–1213.
76.
Hansch GM, Seitz M, Betz M: Effect of the late complement components C5b-9 on human monocytes: Release of prostanoids, oxygen radicals and of a factor inducing cell proliferation. Int Arch Allergy Appl Immunol 1987;82:317–320.
77.
Lovett DH, Haensch GM, Goppelt M, Resch K, Gemsa D: Activation of glomerular mesangial cells by the terminal membrane attack complex of complement. J Immunol 1987;138:2473–2480.
78.
Schonermark M, Deppisch R, Riedasch G, Rother K, Hansch GM: Induction of mediator release from human glomerular mesangial cells by the terminal complement components C5b-9. Int Arch Allergy Appl Immunol 1991;96:331–337.
79.
Solvik UO, Haraldsen G, Fiane AE, Boretti E, Lambris JD, Fung M, Thorsby E, Mollnes TE: Human serum-induced expression of E-selectin on porcine aortic endothelial cells in vitro is totally complement mediated. Transplantation 2001;72:1967–1973.
80.
Couser WG, Pippin JW, Shankland SJ: Complement (C5b-9) induces DNA synthesis in rat mesangial cells in vitro. Kidney Int 2001;59:905–912.
81.
Rus HG, Niculescu F, Shin ML: Sublytic complement attack induces cell cycle in oligodendrocytes. J Immunol 1996;156:4892–4900.
82.
Halperin JA, Taratuska A, Nicholson-Weller A: Terminal complement complex C5b-9 stimulates mitogenesis in 3T3 cells. J Clin Invest 1993;91:1974–1978.
83.
Niculescu F, Badea T, Rus H: Sublytic C5b-9 induces proliferation of human aortic smooth muscle cells: Role of mitogen activated protein kinase and phosphatidylinositol 3-kinase. Atherosclerosis 1999;142:47–56.
84.
De Vries B, Matthijsen RA, Wolfs TG, Van Bijnen AA, Heeringa P, Buurman WA: Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: Inhibition of late apoptosis and inflammation. Transplantation 2003;75:375–382.
85.
Sato T, Van Dixhoorn MG, Prins FA, Mooney A, Verhagen N, Muizert Y, Savill J, Van Es LA, Daha MR: The terminal sequence of complement plays an essential role in antibody-mediated renal cell apoptosis. J Am Soc Nephrol 1999:10:1242–1252.
86.
Bellamy CO, Malcomson RD, Harrison DJ, Wyllie AH: Cell death in health and disease: The biology and regulation of apoptosis. Semin Cancer Biol 1995;6:3–16.
87.
Cohen JJ: Apoptosis. Immunol Today 1993;14:126–130.
88.
Reed JC: Bcl-2 family proteins. Oncogene 1998;17:3225–3236.
89.
Lockshin RA, Zakeri Z: Caspase-independent cell deaths. Curr Opin Cell Biol 2002;14:727–733.
90.
Duvall E, Wyllie AH, Morris RG: Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunology 1985;56:351–358.
91.
Russell L, Waring P, Beaver JP: Increased cell surface exposure of fucose residues is a late event in apoptosis. Biochem Biophys Res Commun 1998;250:449–453.
92.
Waldmeier PC: Prospects for antiapoptotic drug therapy of neurodegenerative diseases. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:303–321.
93.
Dianzani U, Chiocchetti A, Ramenghi U: Role of inherited defects decreasing Fas function in autoimmunity. Life Sci 2003;72:2803–2824.
94.
Walport MJ: Complement. Second of two parts. N Engl J Med 2001;344:1140–1144.
95.
Wyllie AH: Apoptosis and carcinogenesis. Eur J Cell Biol 1997;73:189–197.
96.
Gewurz H, Zhang XH, Lint TF: Structure and function of the pentraxins. Curr Opin Immunol 1995;7:54–64.
97.
Baumann H, Gauldie J: The acute phase response. Immunol Today 1994;15:74–80.
98.
Steel DM, Whitehead AS: The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein. Immunol Today 1994;15:81–88.
99.
Kolb-Bachofen V: A review on the biological properties of C-reactive protein. Immunobiology 1991;183:133–145.
100.
Pepys MB, Baltz ML: Acute phase proteins with special reference to C-reactive protein and related proteins (pentraxins) and serum amyloid A protein. Adv Immunol 1983;34:141–212.
101.
Du Clos TW: Function of C-reactive protein. Ann Med 2000;32:274–278.
102.
Ballou SP, Lozanski G: Induction of inflammatory cytokine release from cultured human monocytes by C-reactive protein. Cytokine 1992;4:361–368.
103.
Griselli M, Herbert J, Hutchinson WL, Taylor KM, Sohail M, Krausz T, Pepys MB: C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med 1999;190:1733–1740.
104.
Xia D, Samols D: Transgenic mice expressing rabbit C-reactive protein are resistant to endotoxemia. Proc Natl Acad Sci USA 1997;94:2575–2580.
105.
Ahmed N, Thorley R, Xia D, Samols D, Webster RO: Transgenic mice expressing rabbit C-reactive protein exhibit diminished chemotactic factor-induced alveolitis. Am J Respir Crit Care Med 1996;153:1141–1147.
106.
Zhong W, Zen Q, Tebo J, Schlottmann K, Coggeshall M, Mortensen RF: Effect of human C-reactive protein on chemokine and chemotactic factor-induced neutrophil chemotaxis and signaling. J Immunol 1998;161:2533–2540.
107.
Baltz ML, Caspi D, Evans DJ, Rowe IF, Hind CR, Pepys MB: Circulating serum amyloid P component is the precursor of amyloid P component in tissue amyloid deposits. Clin Exp Immunol 1986;66:691–700.
108.
Bickerstaff MC, Botto M, Hutchinson WL, Herbert J, Tennent GA, Bybee A, Mitchell DA, Cook HT, Butler PJ, Walport MJ, Pepys MB: Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat Med 1999;5:694–697.
109.
Burlingame RW, Volzer MA, Harris J, Du Clos TW: The effect of acute phase proteins on clearance of chromatin from the circulation of normal mice. J Immunol 1996;156:4783–4788.
110.
Noursadeghi M, Bickerstaff MC, Gallimore JR, Herbert J, Cohen J, Pepys MB: Role of serum amyloid P component in bacterial infection: protection of the host or protection of the pathogen. Proc Natl Acad Sci USA 2000;97:14584–14589.
111.
Botto M, Hawkins PN, Bickerstaff MC, Herbert J, Bygrave AE, McBride A, Hutchinson WL, Tennent GA, Walport MJ, Pepys MB: Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene. Nat Med 1997;3:855–859.
112.
Mold C, Rodriguez W, Rodic-Polic B, Du Clos TW: C-reactive protein mediates protection from lipopolysaccharide through interactions with Fc gamma R. J Immunol 2002;169:7019–7025.
113.
Bharadwaj D, Stein MP, Volzer M, Mold C, Du Clos TW: The major receptor for C-reactive protein on leukocytes is fcgamma receptor II. J Exp Med 1999;190:585–590.
114.
Bharadwaj D, Mold C, Markham E, Du Clos TW: Serum amyloid P component binds to Fc gamma receptors and opsonizes particles for phagocytosis. J Immunol 2001;166:6735–6741.
115.
Stein MP, Edberg JC, Kimberly RP, Mangan EK, Bharadwaj D, Mold C, Du Clos TW: C-reactive protein binding to FcgammaRIIa on human monocytes and neutrophils is allele-specific. J Clin Invest 2000;105:369–376.
116.
Hundt M, Zielinska-Skowronek M, Schmidt RE: Lack of specific receptors for C-reactive protein on white blood cells. Eur J Immunol 2001;31:3475–3483.
117.
Saeland E, van Royen A, Hendriksen K, Vile-Weekhout H, Rijkers GT: Sanders, LA, van de Winkel, JG., Human C-reactive protein does not bind to FcgammaRIIa on phagocytic cells. J Clin Invest 2001;107:641–643.
118.
Alles VV, Bottazzi B, Peri G, Golay J, Introna M, Mantovani A: Inducible expression of PTX3, a new member of the pentraxin family, in human mononuclear phagocytes. Blood 1994;84:3483–3493.
119.
Breviario F, d’Aniello EM, Golay J, Peri G, Bottazzi B, Bairoch A, Saccone S, Marzella R, Predazzi V, Rocchi M, Della Valle G, Dejana E, Mantovani A, Introna M: Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component. J Biol Chem 1992;267:22190–22197.
120.
Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M, Nota R, Maccagno A, Riva F, Bottazzi B, Peri G, Doni A, Vago L, Botto M, De Santis R, Carminati P, Siracusa G, Altruda F, Vecchi A, Romani L, Mantovani A: Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 2002;420:182–186.
121.
Bottazzi B, Vouret-Craviari V, Bastone A, De Gioia L, Matteucci C, Peri G, Spreafico F, Pausa M, D’Ettorre C, Gianazza E, Tagliabue A, Salmona M, Tedesco F, Introna M, Mantovani A: Multimer formation and ligand recognition by the long pentraxin PTX3. Similarities and differences with the short pentraxins C-reactive protein and serum amyloid P component. J Biol Chem 1997;272:32817–32823.
122.
Rovere P, Peri G, Fazzini F, Bottazzi B, Doni A, Bondanza A, Zimmermann VS, Garlanda C, Fascio U, Sabbadini MG, Rugarli C, Mantovani A, Manfredi AA: The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells. Blood 2000;96:4300–4306.
123.
Ravizza T, Moneta D, Bottazzi B, Peri G, Garlanda C, Hirsch E, Richards GJ, Mantovani A, Vezzani A: Dynamic induction of the long pentraxin PTX3 in the CNS after limbic seizures: Evidence for a protective role in seizure-induced neurodegeneration. Neuroscience 2001;105:43–53.
124.
Dias AA, Goodman AR, Dos Santos JL, Gomes RN, Altmeyer A, Bozza PT, Horta MF, Vilcek J, Reis LF: TSG-14 transgenic mice have improved survival to endotoxemia and to CLP-induced sepsis. J Leukoc Biol 2001;69:928–936.
125.
Souza DG, Soares AC, Pinho V, Torloni H, Reis LF, Teixeira MM, Dias AA, Martins MT: Increased mortality and inflammation in tumor necrosis factor-stimulated gene-14 transgenic mice after ischemia and reperfusion injury. Am J Pathol 2002;160:1755–1765.
126.
Peri G, Introna M, Corradi D, Iacuitti G, Signorini S, Avanzini F, Pizzetti F, Maggioni AP, Moccetti T, Metra M, Cas LD, Ghezzi P, Sipe JD, Re G, Olivetti G, Mantovani A, Latini R: PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans. Circulation 2000;102:636–641.
127.
Luchetti MM, Piccinini G, Mantovani A, Peri G, Matteucci C, Pomponio G, Fratini M, Fraticelli P, Sambo P, Di Loreto C, Doni A, Introna M, Gabrielli A: Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA). Clin Exp Immunol 2000;119:196–202.
128.
Muller B, Peri G, Doni A, Torri V, Landmann R, Bottazzi B, Mantovani A: Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients. Crit Care Med 2001;29:1404–1407.
129.
Napoleone E, Di Santo A, Bastone A, Peri G, Mantovani A, de Gaetano G, Donati MB, Lorenzet R: Long pentraxin PTX3 upregulates tissue factor expression in human endothelial cells: a novel link between vascular inflammation and clotting activation. Arterioscler Thromb Vasc Biol 2002;22:782–787.
130.
Reid MS, Blobel CP: Apexin, an acrosomal pentaxin. J Biol Chem 1994;269:32615–32620.
131.
Seery LT, Schoenberg DR, Barbaux S, Sharp PM, Whitehead AS: Identification of a novel member of the pentraxin family in Xenopus laevis. Proc R Soc Lond B Biol Sci 1993;253:263–270.
132.
Schlimgen AK, Helms JA, Vogel H, Perin MS: Neuronal pentraxin, a secreted protein with homology to acute phase proteins of the immune system. Neuron 1995;14:519–526.
133.
Hsu YC, Perin MS: Human neuronal pentraxin II (NPTX2): conservation, genomic structure, and chromosomal localization. Genomics 1995;28:220–227.
134.
Tsui CC, Copeland NG, Gilbert DJ, Jenkins NA, Barnes C, Worley PF: Narp, a novel member of the pentraxin family, promotes neurite outgrowth and is dynamically regulated by neuronal activity. J Neurosci 1996;16:2463–2478.
135.
Roos A, Trouw LA, Ioan-Facsinay A, Daha MR, Verbeek JS: Complement System: Genetics. Nature Encyclopedia of the Human Genome. Macmillan Publishers Ltd., Nature Publishing Group, 2003, pp 914–927.
136.
O’Neil KM: Complement deficiency. Clin Rev Allergy Immunol 2000;19:83–108.
137.
Albert ML, Sauter B, Bhardwaj N: Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998;392:86–89.
138.
Bellone M, Iezzi G, Rovere P, Galati G, Ronchetti A, Protti MP, Davoust J, Rugarli C, Manfredi AA: Processing of engulfed apoptotic bodies yields T cell epitopes. J Immunol 1997;159:5391–5399.
139.
Rovere P, Sabbadini MG, Vallinoto C, Fascio U, Zimmermann VS, Bondanza A, Ricciardi-Castagnoli P, Manfredi AA: Delayed clearance of apoptotic lymphoma cells allows cross-presentation of intracellular antigens by mature dendritic cells. J Leukoc Biol 1999;66:345–349.
140.
Weiser MR, Williams JP, Moore FD Jr, Kobzik L, Ma M, Hechtman HB, Carroll MC: Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement. J Exp Med 1996;183:2343–2348.
141.
Williams JP, Pechet TT, Weiser MR, Reid R, Kobzik L, Moore FD Jr, Carroll MC, Hechtman HB: Intestinal reperfusion injury is mediated by IgM and complement. J Appl Physiol 1999;86:938–942.
142.
Zhou W, Farrar CA, Abe K, Pratt JR, Marsh JE, Wang Y, Stahl GL, Sacks SH: Predominant role for C5b-9 in renal ischemia/reperfusion injury. J Clin Invest 2000;105:1363–1371.
143.
Pratt JR, Basheer SA, Sacks SH: Local synthesis of complement component C3 regulates acute renal transplant rejection. Nat Med 2002;8:582–587.
144.
Asghar SS, Pasch MC: Therapeutic inhibition of the complement system. Y2K update. Front Biosci 2000;5:E63–E81.
145.
Caliezi C, Wuillemin WA, Zeerleder S, Redondo M, Eisele B, Hack CE: C1-Esterase inhibitor: An anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema. Pharmacol Rev 2000;52:91–112.
© 2004 S. Karger AG, Basel
2004
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.