Conclusions
The molecular mechanisms of the alternative pathway are now reasonably well understood. Intramolecular functional sites are currently being delineated that govern the crucial interactions between C3 and the other proteins of the pathway. The knowledge of the primary structure of C3 is affording the synthesis of small peptides that may aid the identification of functional regions. Should the three-dimensional structure of C3 or C3b become available, information on functional regions may readily be incorporated into the molecular model. Uncertain remains the mechanism of recognition utilized by the alternative pathway to distinguish between activators and nonactivators. This ability resides in C3b and Factor H which jointly constitute the recognition unit. But how this simple bimolecular recognition unit senses cell surface structures is unknown. The relatively recent awareness of cell surface regulators of complement has led to the description of a molecular defect in an acquired hemolytic anemia. The biologic role of these membrane proteins and their occurrence on cells other than erythrocytes will have to be determined. Also, both CRI and DAF share functional properties with Factor H and C4 binding protein and it is probable that the functional homologies have structural correlates. Thus these four proteins together with properdin constitute a group of apparently interrelated binding proteins that function as regulators of the C3/C5 convertases. Structural information on the protein or cDNA level is needed to assess the degree of interrelatedness between these plasma and membrane proteins.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Albar JP, Juarez C, Vivanco-Martinez F, Bragado R, Ortiz F (1981) Structural requirements of rabbit IgG F(ab'⊃2 fragment for activation of the complement system through the alternative pathway. I. Disulfide bonds. Mol Immunol 18: 925
Berger MM, Gaither TA, Hammer CH, Frank MM (1981) Lack of binding of human C3, in its native state, to C3b receptors. J Immunol 127: 1329
Campbell RD, Porter RR (1983) Molecular cloning and characterization of the gene coding for human complement Factor B. Proc Natl Acad Sci USA 80: 4464
Capel PJA, Groeneboer O, Grosveld G, Pondmann KW (1978) The binding of activated C3 to polysaccharides and immunoglobulins. J Immunol 121: 2566
Cochrane CG, Müller-Eberhard HJ, Aikin BS (1970) Depletion of plasma complement in vivo by a protein of cobra venom: its effect on various immunologic reactions. J Immunol 105: 55
Cooper NR (1973) Activation of the complement system. Contemp Top Mol Immunol 2: 155
Cooper NR, Currie MS, Rustagi PK (1983) T-lymphocytes escape defect in paroxysmal nocturnal hemoglobinuria. Br J Haematol 55: 263
Cornacoff JB, Hebert LA, Smead WL, VanAman ME, Birmingham DJ, Waxman FJ (1983) Primate erythrocyte-immune complex-clearing mechanism. J Clin Invest 71: 236
Crossley LG, Porter RR (1980) Purification of the human complement control protein C3b inactivator. Biochem J 191: 173
Dacie JV, Richardson N (1943) The influence of pH on in vitro haemolysis in nocturnal heamoglobinuria. J Pathol Bacteriol 55: 375
Daha MR, Fearon DT, Austen KF (1976) Requirements for formation of alternative pathway C5 convertase. J Immunol 117: 630
Dalmasso AP, Müller-Eberhard HJ (1966) Hemolytic activity of lipoprotein-depleted serum and the effect of certain anions on complement. J Immunol 97: 680
Davis AE, Harrison RA (1982) Structural characterization of Factor I mediated cleavage of the third component of complement. Biochemistry 21: 5745
Davis AE, Harrison RA, Lachmann PJ (1984) Physiologic inactivation of fluid phase C3b: isolation and structural analysis of C3c, C3dg (α2D), and C3g. J Immunol 132: 1960
DiScipio RG (1981) The binding of human complement proteins C5, Factor B,β1H and properdin to complement fragment C3b on zymosan. Biochem J 199: 485
DiScipio RG (1982) Properdin is a trimer. Mol Immunol 19: 631
Dykman TR, Cole JL, Iida K, Atkinson JP (1983) Polymorphism of human erythrocyte C3b/C4b receptor. Proc Natl Acad Sci USA 80: 1698
Edwards MS, Kasper DL, Jennings HF, Baker CJ, Nicholson-Weller A (1982) Capsular sialic acid prevents activation of the alternative complement pathway by type III, group B streptococci. J Immunol 128: 1278
Fearon DT (1978) Regulation by membrane sialic acid ofβ1H-dependent decay-dissociation of amplification C3 convertase of the alternative complement pathway. Proc Natl Acad Sci USA 75: 1971
Fearon DT (1979) Regulation of the amplification C3 convertase of human complement by an inhibitory protein isolated from human erythrocyte membrane. Proc Natl Acad Sci USA 76: 5867
Fearon DT (1980) Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J Exp Med 152: 20
Fearon DT, Austen KF (1975) Initiation of C3 cleavage in the alternative complement pathway. J Immunol 115: 1357
Fearon DT, Austen KF (1975) Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase. J Exp Med 142: 856
Fearon DT, Austen KF (1977) Activation of the alternative complement pathway due to resistance of zymosan-bound amplification convertase to endogenous regulatory mechanisms. Proc Natl Acad Sci USA 74: 1683
Fearon DT, Austen KF (1977) Activation of the alternative complement pathway with rabbit erythrocytes by circumvention of the regulatory action of endogenous control proteins. J Exp Med 146: 22
Fearon DT, Austen KF, Ruddy S (1974) Properdin Factor D: characterization of its active site and isolation of the precursor form. J Exp Med 139: 355
Fischer E, Kazatchkine MD (1983) Surface-dependent modulation by H of C5 cleavage by the cell-bound alternative pathway C5 convertase of human complement. J Immunol 130: 2821
Fishelson Z, Müller-Eberhard HJ (1982) C3 convertase of human complement: enhanced formation and stability of the enzyme generated with nickel instead of magnesium. J Immunol 129: 2603
Fishelson Z, Müller-Eberhard HJ (1984) Residual hemolytic and proteolytic activity expressed by Bb after decay-dissociation of C3b,Bb. J Immunol 132: 1425
Fishelson Z, Lambris JD, Müller-Eberhard HJ (submitted for publication) C3 convertase of the human alternative pathway of complement: modulation of enzyme activity and stability by murine monoclonal antibodies to Bb.
Fishelson Z, Pangburn MK, Müller-Eberhard HJ (1983) C3 convertase of the alternative complement pathway: demonstration of an active, stable C3b, Bb(Ni) complex. J Biol Chem 258: 7411
Fishelson Z, Pangburn MK, Müller-Eberhard HJ (1984) Characterization of the initial C3 convertase of the alternative pathway of human complement. J Immunol 132: 1430
Fishelson Z, Schreiber RD, Pangburn MK, Müller-Eberhard HJ (to be published) Complement regulatory functions of the C3b receptor: regulation of C5 convertase activity.
Fujita T, Nussenzweig V (1979) The role of C4-binding protein andβ1H in proteolysis of C4b and C3b. J Exp Med 150: 267
Fujita T, Gigli I, Nussenzweig V (1978) Human C4 binding protein II. Role in proteolysis of C4 inactivator. J Exp Med 148: 1044
Gann V, Fernandez-Cruz E, Müller-Eberhard HJ (1984) Synthesis and properties of a monoclonal antibody-cobra venom factor complex which is stable in vivo. Fed Proc 43: 1772 (abstract)
Gigli I, Fujita T, Nussenzweig V (1979) Modulation of the classical pathway C3 convertase by plasma proteins, C4 binding protein and C3b inactivator Proc Natl Acad Sci USA 76: 6596
Götze O, Müller-Eberhard HJ (1970) Lysis of erythrocytes by complement in the absence of antibody. J Exp Med 132: 898
Götze O, Müller-Eberhard HJ (1971) The C3-activator system: an alternative pathway of complement activation. J Exp Med 134: 90s
Götze O, Müller-Eberhard HJ (1976) The alternative pathway of complement activation. Adv Immunol 24: 1
Götze O, Medicus RG, Müller-Eberhard HJ (1977) Alternative pathway of complement: nonenzymatic, reversible transition of precursor to active properdin. J Immunol 118: 525
Götze O, Bianco C, Cohn ZA (1979) The induction of macrophage spreading by Factor B of properdin system. J Exp Med 149: 372
Hammer CH, Hansch G, Gresham HD, Shin ML (1983) Activation of the fifth and sixth components of the human complement system: C6-dependent cleavage of C5 in acid and the formation of a bimolecular lytic complex, C5b, 6a. J Immunol 130: 892
Hansch GM, Hammer C, Tiji R, Rother U, Shin M (1983) Lysis of paroxysmal nocturnal hemaglobinuria erythrocytes by acid-activated serum. Immunobiology 164: 118
Harrison RA, Lachmann PJ (1980) The physiological breakdown of the third component of human complement. Mol Immunol 17: 9
Hirani S, Lambris JD, Mülller-Eberhard HJ (in press) Localization of the bovine conglutinin binding site on the third component of complement. J Immunol
Hoffmann EM (1969) Inhibition of complement by a substance isolated from human erythrocytes. I. Extraction from human erythrocyte stromata. Immunochemistry 6: 391
Hoffmann EM (1969) Inhibition of complement by a substance isolated from human erythrocytes. II. Studies on the site and mechanism of action. Immunochemistry 6: 405
Hoffmann EM, Etlinger HM (1973) Extraction of complement inhibitory factors from the erythrocytes of non-human species. J Immunol 111: 946
Horstmann RD, Müller-Eberhard HJ (in press) Isolation of rabbit C3, Factor B and Factor H and comparison of their properties with those of the human analogues. J Immunol
Horstmann RD, Pangburn MK, Müller-Eberhard HJ (in press) Species specificity of recognition by the alternative pathway of complement. J Immunol
Horstmann RD, Pangburn MK, Müller-Eberhard HJ (submitted for publication) Active participation of Factor H in the recognition function of the alternative pathway of complement.
Hostetter MK, Thomas ML, Rosen FS, Tack BF (1982) Binding of C3b proceeds by a transesterification reaction at the thiolester site. Nature 298: 72
Hsiung L, Barclay AN, Gagnon J, Brandon MR, Porter RR (1982) The C3b inactivator is a serine protease. Mol Immunol 19: 1376 (abstract)
Iida K, Nussenzweig V (1981) Complement receptor is an inhibitor of the complement cascade. J Exp Med 153: 1138
Iida K, Nussenzweig V (1983) Functional properties of membrane-associated complement receptor CR1. J Immunol 130: 1876
Isenman DE, Cooper NR (1981) The structure and function of the third component of human complement. I. The nature and extent of conformational changes accompanying C3 activation. Mol Immunol 18: 331
Isenman DE, Podack ER, Cooper NR (1980) The interaction of C5 with C3b in free solution: a sufficient condition for cleavage by fluid phase C3/C5 convertase. J Immunol 124: 326
Isenmann DE, Kells DIC, Cooper NR, Müller-Eberhard HJ, Pangburn MK (1981) Nucleophilic modification of human complement protein C3: correlation of conformational changes with acquisition of C3b-like functional properties. Biochemistry 20: 4458
Janatova J, Tack BF, Prahl JW (1980) Third component of human complement: structural requirements for its function. Biochemistry 19: 4479
Janatova J, Lorenz PE, Schechter AN, Prahl JW, Tack BF (1980) Third component of human complement: appearance of a sulfhydryl group following chemical or enzymatic inactivation. Biochemistry 19: 4471
Johnson MS, Gagnon J, Reid KBM (1980) Factor D of the alternative pathway of human complement. Purification, alignment and N-terminal amino acid sequences of the major cyanogen bromide fragments, and localization of the serine residue at the active site. Biochem J 187: 863
Johnson DMA, Gagnon J, Reid KBM (1984) Amino acid sequence of human Factor D of the complement system. Similarity in sequence between Factor D and proteases of non-plasma origin. FEBS Lett 166: 347
Jones CM, Shin ML, Mayer MM (1982) On lysis of paroxysmal nocturnal hemoglobinuria erythrocytes by complement: dual role of C3b. Blut 45: 249
Kazatchkine MD, Fearon DT, Austen KF (1979) Human alternative complement pathway: membrane-associated sialic acid regulates the competition between B andβ1H for cell-bound C3b. J Immunol 122: 75
Kazatchkine MD, Fearon DT, Silbert JE, Austen KF (1979) Surface-associated heparin inhibits zymosan-induced activation of the human alternative pathway by augmenting the regulatory action of the control proteins on particle-bound C3b. J Exp Med 50: 1202
Khan SA, Erickson BW (1981) Synthesis of macrocyclic peptide tiolactones as models of the metastable binding sites of α2-macroglobulin and complement proteins C3b. J Am Chem Soc 103: 7374
Khan SA, Erickson BW (1982) An equilibrium model of the metastable binding sites of α2- macroglobulin and complement proteins C3 and C4. J Biol Chem 257: 11864
Khan SA, Erickson BW, Müller-Eberhard HJ, Pangburn MK (1981) Synthetic peptides containing the macrocyclic thiolester Cys-Gly-Glu-Glu: models of the metastable binding site of human complement protein C3b. In: Rich DH, Gross E (eds) Peptides: Synthesis-structure-function. Pierce Chemical Company, Rockford, p 553.
Khan SA, Pangburn MK, Müller-Eberhard HJ, Erickson BW (1981) The cyclic thioester form of a synthetic hexapeptide from human complement protein C3 resembles the C3b metastable binding site. Fed Proc 40. 1679
Lachmann PJ, Halbwachs L (1975) The influence of C3b inactivator (KAF) concentration on the ability of serum to support complement activation. Clin Exp Immunol 21: 109
Lachmann PJ, Mülller-Eberhard HJ (1968) The demonstration in human serum of “conglutinogen activating factor” and its effect on the third component of complement. J Immunol 100: 691
Lachmann PJ, Rosen FS (1978) Genetic defects of complement in man. Springer Semin Immunopathol 1: 339
Lachmann PJ, Pangburn MK, Oldroyd RG (1982) Breakdown of C3 after complement activation. Identification of a new fragment, C3g, using monoclonal antibodies. J Exp Med 156: 205
Lambris JD, Müller-Eberhard HJ (in press) Isolation and characterization of a 33000 dalton fragment of complement Factor B with catalytic and C3b binding activity. J Biol Chem
Lambris JD, Alsenz J, Schulz TF, Dierich MP (1984) Mapping of the properdin-binding site in the third component of complement. Biochem J 217: 323
LaMotte GB, Tamerius JD, Müller-Eberhard HJ (1981) Monoclonal antibodies to human Factor B and to a neoantigen characteristic for its Bb fragment. Fed Proc 40: 963 (abstract)
Law SK, Levine RP (1977) Interaction between the third complement protein and cell surface. Proc Natl Acad Sci USA 74: 2701
Law SK, Lichtenberg NA, Levine RP (1979) Evidence for an ester linkage between the labile binding site of C3b and receptive surfaces. J Immunol 123: 1388
Law SK, Lichtenberg NA, Levine RP (1980) Covalent binding and hemolytic activity of complement proteins. Proc Natl Acad Sci USA 77: 7194
Law SA, Minich TM, Levine RP (1981) Binding reaction between the third human complement protein and small molecules. Biochemistry 20: 7457
Leibowitz AI, Hartmann RC (1981) The Budd-chairi syndrome and paroxysmal nocturnal hemoglobinuria. Br J Haematol 48: 1
Lesavre P, Müller-Eberhard HJ (1978) Mechanism of action of Factor D of the alternative complement pathway. J Exp Med 148: 1498
Lesavre PH, Hugh TE, Esser AF, Müller-Eberhard HJ (1979) The alternative pathway C3/C5 convertase: chemical basis of Factor B activation. J Immunol 123: 529
Logue GL, Rosse WF, Adams JP (1973) Mechanism of immune lysis of red blood cells in vitro. I. PNH cells. J Clin Invest 52: 1129
Lublin DM, Grumet FC (1982) Mechanism of enhanced complement-dependent cytotoxicity of papain-treated lymphocytes: evidence for increased stability of classical pathway C3 convertase. J Immunol 128: 866
Lundwall A, Hellman U, Eggertsen G, Sjöquist J (1984) Chemical characterization of cyanogen bromide fragments from theβ-chain of human complement Factor C3. FEBS Lett 169: 57
Mann J, O'Brien R, Hostetter MK, Alper CA, Rosen FS, Babior BM (1981) The third comonent of complement: covalent attachment of a radioactive sugar to the labile binding site of C3 via the alternative pathway. J Immunol 126: 2370
Medicus RG, Arnaout MA (1982) Release of C3c from bound C3bi by C3b inactivator. Mol Immunol 19: 1386 (abstract)
Medicus RG, Arnaout MA (1982) Surface restricted control of C3b INA-dependent C3c release from bound C3bi molecules. Fed Proc 41: 848 (abstract)
Medicus RG, Götze O, Müller-Eberhard HJ (1976) Alternative pathway of complement: recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of the pathway. J Exp Med 144: 1076
Medicus RG, Götze O, Müller-Eberhard HJ (1976) The serine protease nature of the C3 and C5 convertases of the classical and alternative complement pathways. Scand J Immunol 5: 1049
Medicus RG, Schreiber RD, Götze O, Müller-Eberhard HJ (1976) A molecular concept of the properdin pathway. Proc Natl Acad Sci USA 73: 612
Medicus RG, Esser AF, Fernandez HN, Müller-Eberhard HJ (1980) Native and activated properdin: interconvertibility and identity of amino-carboxy-terminal sequences. J Immunol 124: 602
Medicus RG, Melamed J, Arnaout MA (1983) The role of human Factor I and C3b receptor in the cleavage of surface-bound C3bi molecules. Eur J Immunol 13: 465
Medof ME, Oger JJ-F (1982) Competition for immune complexes by red cells in human blood. J Clin Lab Immunol 7: 7
Medof ME, Prince GM, Mold C (1982) Release of soluble immune complexes from immune adherence receptors on human erythrocytes is mediated by C3b inactivator independently ofβ1H and is accompanied by generation of C3c. Proc Natl Acad Sci USA 79: 5047
Medof ME, Iida K, Mold C, Nussenzweig V (1982) Unique role of the complement receptor CR1 in the degredation of C3b associated with immune complexes. J Exp Med 156: 1739
Medof ME, Lam T, Prince GM, Mold C (1983) Requirement for human red blood cells in inactivation of C3b in immune complexes and enhancement of binding to spleen cells. J Immunol 130: 1336
Minta JO, Lepow TH (1974) Studies on the subunit structure of human properdin. Immunochemistry 11: 361
Mole JE, Woods D, Colten H, Anderson JK (1983) Completion of the primary structures of the Ba and Bb fragments of Factor B and construction of the final amino acid sequence for the zymogen. Immunobiology 164: 279 (abstract)
Müller-Eberhard HJ, Götze O (1972) C3 proactivator convertase and its mode of action. J Exp Med 135:1003
Müller-Eberhard HJ, Nilsson U (1960) Relation of aβ 1-glycoprotein of human serum to the complement system. J Exp Med 111: 217
Müller-Eberhard HJ, Schreiber RD (1980) Molecular biology and chemistry of the alternative pathway of complement. Adv Immunol 29: 1
Müller-Eberhard HJ, Dalmasso AP, Calcott MA (1966) The reaction mechanism ofβ1C-globulin (C′3) in immune hemolysis. J Exp Med 123: 33
Nagasawa S, Stroud RM (1977) Mechanism of action of the C3b inactivator: requirement for a high molecular weight cofactor (C3b-C4bINA cofactor) and production of a new C3b derivative (C3b′). Immunochemistry 14: 749
Nicholson-Weller A, Burge J, Fearon DT, Weller PF, Austen KF (1982) Isolation of a human erythrocyte membrane glycoprotein with decay-accelerating activity for C3 convertases of the complement system. J Immunol 129: 184
Nicholson-WellerA, March JP, Rosenfeld SI, Austen KF (1983) Affected erythrocytes of patients with paroxysmal nocturnal hemoglobinuria are deficient in the complement regulatory protein, decay accelerating factor. Proc Natl Acad Sci USA 80: 5066
Nicol PAE, Lachmann PJ (1973) The alternative pathway of complement activation. The role of C3 and its inactivator (KAF). Immunology 24: 259
Nilsson UR, Müller-Eberhard HJ (1965) Isolation ofβ →F-globulin from human serum and its characterization as the fifth component of complement. J Exp Med 122: 277
Nydegger UE, Fearon DT, Austen KF (1978) Autosomal locus regulates inverse relationship between sialic acid content and capacity of mouse erythrocytes to activate human alternative complement pathway. Proc Natl Acad Sci USA 75: 6078
Okada H, Tanaka H (1983) Species-specific inhibition by glycophorin of complement activation via the alternative pathway. Mol Immunol 20: 1233
Okada N, Yasuda T, Okada H (1982) Restriction of alternative complement pathway activation by sialosylglycolipids. Nature 299: 261
Okada N, Yasuda T, Tsumita T, Okada H (1982) Activation of the alternative complement pathway of guinea pig by liposomes incorporated with trinitropheylated phosphatidylethanolamine. Immunology 45: 115
Okada H, Yasuda T, Tsumita T, Okada H (1983) Membrane sialoglycolipids regulate the activation of the alternative complement pathway by liposomes containing trinitrophenylaminocaproxyldipalmitoylphosphatydylethanolamine. Immunology 48: 129
Packman CH, Rosenfeld SI, Jenkins DE, Thiem PA, Leddy JP (1979) Complement lysis of human erythrocytes: differing susceptibilities of two types of paroxysmal nocturnal hemoglobinuria cells to C5b-9. J Clin Invest 64: 428
Pangburn MK (1983) Activation of complement via the alternative pathway. Fed Proc 42: 139
Pangburn MK, Müller-Eberhard HJ (1978) Complement C3 convertase: cell surface restriction ofβ1H control and generation of restriction on neuraminidase treated cells. Proc Natl Acad Sci USA 75: 2416
Pangburn MK, Müller-Eberhard HJ (1980) Relation of a putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement. J Exp Med 152: 1102
Pangburn MK, Müller-Eberhard HJ (1982) Kinetic and thermodynamic analysis of the control of C3b by the complement regulatory proteins Factor H and Factor I. Biochemistry 22: 178
Pangburn MK, Müller-Eberhard HJ (1983) Characteristics of a complement C3 convertase: kinetic analysis of C3 cleavage using a fluorometric assay. Fed Proc 42: 2075 (abstract)
Pangburn MK, Müller-Eberhard HJ (to be published) The C3 convertase of the alternative pathway of human complement: kinetic analysis of a biomolecular protease
Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1977) Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum proteinβ1H for cleavage of C3b and Cob in solution. J Exp Med 146: 257
Pangburn MK, Morrison DC, Schreiber RD, Müller-Eberhard HJ (1980) Activation of the alternative complement pathway: recognition of surface structures on activators by bound C3b. J Immunol 124:977
Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1981) Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous hydrolysis of the putative thioester in native C3. J Exp Med 154: 856
Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1983) C3b deposition during activation of the alternative complement pathway and the effect of deposition on the activating surface. J Immunol 131: 1930
Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1983) Deficiency of an erythrocyte membrane protein with complement regulatory activity in paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci USA 80: 5430
Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1983) Regulation of complement by human erythrocyte membrane-associated proteins: deficiency in paroxysmal nocturnal hemoglobinuria. Immunobiology 164: 283 (abstract)
Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1983) Paroxysmal nocturnal hemoglobinuria: lack of a regulator of complement activation on the abnormal erythrocytes. Blood 62: 105a (abstract)
Pangburn MK, Schreiber RD, Trombold JS, Müller-Eberhard HJ (1983) Paroxysmal nocturnal hemoglobinuria: deficiency in Factor H-like functions of the abnormal erythrocytes. J Exp Med 157:1971
Pangburn MK, Schreiber RD, Müller-Eberhard HJ (submitted- for publication) Characterization of the complement regulatory functions of the decay accelerating factor and the C3b receptor on normal human erythrocytes.
Parkes C, DiScipio RG, Kerr MA, Prohaska R (1981) The separation of functionally distinct forms of the third component of human complement (C3). Biochem J 193: 963
Pensky J, Hinz CF, Todd EW, Wedgwood RJ, Boyer JT, Lepow IH (1968) Properties of highly purified human properdin. J Immunol 100: 142
Pillemer L, Blum L, Lepow IH, Ross OA, Todd EW, Wardlaw AC (1954) The properdin system and immunity. I. Demonstration and isolation of a new serum protein, properdin, and its role in immune phenomena. Science 120: 279
Ratnoff WD, Fearon DT, Austen KF (1984) The role of antibody in the activation of the alternative complement pathway. Springer Semin Immunopathol 6: 361
Reid KBM, Gagnon J (1981) Amino acid sequence studies of human properdin-N-terminal sequence analysis and alignment of the fragments produced by limited proteolysis with trypsin and the peptides produced by cyanogen bromide treatment. Mol Immunol 18: 949
Rosenfeld SI, Jenkins DE, Leddy JP (1984) Paroxysmal nocturnal hemoglobinuria erythrocytes (PNH E): enhanced lysis by terminal complement components with no increase in C7 binding. Fed Proc 43: 1766
Ross GD, Lambris JD, Cain JA, Newman SL (1982) Generation of three different fragments of bound C3 with purified Factor I or serum. I. Requirements for Factor H vs. CR1 cofactor activity. J Immunol 129: 2051
Rosse WF (1972) Erythrocyte disorders — paroxysmal nocturnal hemoglobinuria. In: Williams WJ, Beutler E, Erselv AJ, Rundles RW (eds) Hematology. McGraw-Hill, New York, p 460
Rosse WE (1978) Paroxysmal nocturnal heamoglobinuria in aplastic anaemia. Clin Haematol 7: 541
Rothman IK, Gelfand JA, Fauci AS, Frank MM (1975) The immune adherence receptor: dissociation between the expression of erythrocytes and mononuclear cell C3b receptor. J Immunol 115:1312
Schreiber RD, Müller-Eberhard HJ (1978) Assembly of the cytolytic alternative pathway of complement from 11 isolated plasma proteins. J Exp Med 148: 1722
Schreiber RD, Medicus RG, Götze O, Müller-Eberhard HJ (1975) Properdin- and nephritic factor-dependent C3 convertases: requirement of native C3 for enzyme formation and the function of bound C3b as properdin receptor. J Exp Med 142: 760
Schreiber RD, Pangburn MK, Lesavre P, Müller-Eberhard HJ (1978) Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins. Proc Natl Acad Sci USA 75: 3948
Schreiber RD, Morrison DC, Podack ER, Müller-Eberhard HJ (1979) Bactericidal activity of the alternative complement pathway generated from eleven isolated plasma proteins. J Exp Med 149: 870
Schreiber RD, Pangburn MK, Müller-Eberhard HJ (1981) C3 modified at the thioester site: acquisition of reactivity with cellular C3b receptors. Biosci Rep 1: 873
Sim RB, Twose TM, Paterson DS, Sim E (1981) The covalent-binding reaction of complement component C3. Biochem J 193: 115
Sim E, Wood AB, Hsiung L, Sim RB (1981) Patterns of degradation of human complement fragment, C3b. FEBS Lett 132: 55
Sissons JGP, Schreiber RD, Perrin LH, Cooper NR, Müller-Eberhard HJ, Oldstone MBA (1979) Lysis of measles virus-infected cells by the purified cytolytic alternative complement pathway and antibody. J Exp Med 150: 445
Sissons JGP, Oldstone MBA, Schreiber RD (1980) Antibody-independent activation of the alternative complement pathway by measles virus-infected cells. Proc Natl Acad Sci USA 77: 559
Smith CA, Vogel C-W, Müller-Eberhard HJ (1982) Ultrastructure of cobra venom factor dependent C3/C5 convertase and its zymogen, Factor B of human complement. J Biol Chem 257: 9879
Smith CA, Vogel C-W, Müller-Eberhard HJ (1983) MHC class III products: an electron microscope study of the C3 convertases of human complement. J Exp Med 159: 324
Smith CA, Pangburn MK, Vogel C-W, Müller-Eberhard HJ (1984) Molecular architecture of human properdin, a positive regulator of the alternative pathway of complement. J Biol Chem 259: 4582
Swenson RP, Howard JB (1979) Characterization of alkylamine ensitive site in a2 macroglobulin. Proc Natl Acad Sci USA 76: 4313
Tack BE, Harrison RA, Janatova J, Thomas ML, Prahl JW (1980) Evidence for presence of an internal thiolester bond in third component of human complement. Proc Natl Acad Sci USA 77: 5764
Vogel C-W, Müller-Eberhard HJ (1981) Induction of immune cytolysis: tumor-cell killing by complement is initiated by covalent complex of monoclonal antibody and stable C3/C5 convertase. Proc Natl Acad Sci USA 78: 7707
Vogel C-W, Müller-Eberhard HJ (1982) The cobra venom factor-dependent C3 convertase of human complement. J Biol Chem 257: 8292
Vogel C-W, Müller-Eberhard HJ (in press) Cobra venom factor: improved method for purification and biochemical characterization. J Immunol Methods
Vogel C-W, Müller-Eberhard HJ (in press) Comparison of C3 of cobra serum with cobra venom factor. J Immunol
Vogel CW, Smith CA, Müller-Eberhard HJ (in press) Cobra venom factor: structural homology with the third component of human complement. J Immunol
Vogt W, Dames W, Schmidt G, Dieminger L (1977) Complement activation by the properdin system: formation of a stoichiometric C3 cleaving complex of properdin factor B and C3b. Immunochemistry 14: 201
Vogt W, Schmidt G, von Buttlar B, Dieminger L (1978) A new function of the activated third component of complement: binding to C5, an essential step for C5 activation. Immunology 34: 29
Volanakis JE, Brown AS, Bennett JC, Mole JE (1980) Partial amino acid sequence of human factor D: homology with serine proteases. Proc Natl Acad Sci USA 77: 1116
VonZabern I, Nolte R, Vogt W (1981) Treatment of human complement components C4 and C3 with amines or chaotropic ions. Scand J Immunol 13: 413
Weiler JM, Daha MR, Austen KF, Fearon DT (1976) Control of the amplification convertase of complement by the plasma proteinβ1H. Proc Natl Acad Sci USA 73: 3268
Wetsel RA, Lundwall A, Davison F, Gibson T, Tack BE, Fey GH (in press) Structure of murine complement component C3 II. Nucleotide sequence of cloned complementary DNA coding for the α chain. J Biol Chem
Whaley K, Ruddy S (1976) Modulation of the alternative complement pathway byβ1H globulin. J Exp Med 144: 1147
Wong WW, Wilson JG, Fearon DG (1983) Genetic regulation of a structural polymorphism of human C3b receptor. J Clin Immunol 72: 685
Ziccardi RJ, Dahlback B, Müller-Eberhard HJ (in press) Characterization of the interaction of human C4b-binding protein (C4BP) with physiologically ligands. J Biol Chem
Author information
Authors and Affiliations
Additional information
This is Publication Number 3573-IMM from the Research Institute of Scripps Clinic
This work was supported by United States Public Health Service Grants AI 17354, CA 27489 and HL 16411
Dr. Müller-Eberhard is the Cecil H. and Ida M. Green Investigator in Medical Research, Research Institute of Scripps Clinic
This work was done during the tenure of an Established Investigatorship (No. 81-225) from the American Heart Association and with funds contributed in part by the A. H. A. California Affiliate
Rights and permissions
About this article
Cite this article
Pangburn, M.K., Müller-Eberhard, H.J. The alternative pathway of complement. Springer Semin Immunopathol 7, 163–192 (1984). https://doi.org/10.1007/BF01893019
Issue Date:
DOI: https://doi.org/10.1007/BF01893019