Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1994 Oct;62(10):4549–4555. doi: 10.1128/iai.62.10.4549-4555.1994

Complement activation by whole endotoxin is blocked by a monoclonal antibody to factor B.

C W Clardy 1
PMCID: PMC303142  PMID: 7927720

Abstract

Sepsis is both a common and, despite present-day therapy, a serious disease. The pathophysiology of the septic response is a complex, multifactorial phenomenon which in part involves the activation of complement by bacterial endotoxin. A monoclonal antibody to human complement factor B, code-named 1H5, which was capable of specifically inhibiting the alternative pathway of complement activation at concentrations as low as 1 microgram/ml, is described. This agent had no effect on the classical pathway of complement activation. It was capable of preventing the activation of complement by even high concentrations (0.1 mg/ml) of whole endotoxin; however, it was ineffective in preventing activation of complement by endotoxin derived from a rough mutant. This agent could potentially be used in the treatment of sepsis.

Full text

PDF
4549

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahearn J. M., Fearon D. T. Structure and function of the complement receptors, CR1 (CD35) and CR2 (CD21). Adv Immunol. 1989;46:183–219. doi: 10.1016/s0065-2776(08)60654-9. [DOI] [PubMed] [Google Scholar]
  2. Asghar S. S. Pharmacological manipulation of complement system. Pharmacol Rev. 1984 Dec;36(4):223–244. [PubMed] [Google Scholar]
  3. Ballow M., Cochrane C. G. Two anticomplementary factors in cobra venom: hemolysis of guinea pig erythrocytes by one of them. J Immunol. 1969 Nov;103(5):944–952. [PubMed] [Google Scholar]
  4. Bengtson A., Heideman M. Anaphylatoxin formation in sepsis. Arch Surg. 1988 May;123(5):645–649. doi: 10.1001/archsurg.1988.01400290131023. [DOI] [PubMed] [Google Scholar]
  5. Boackle R. J., Johnson B. J., Caughman G. B. An IgG primary sequence exposure theory for complement activation using synthetic peptides. Nature. 1979 Dec 13;282(5740):742–743. doi: 10.1038/282742a0. [DOI] [PubMed] [Google Scholar]
  6. Boenisch T., Alper C. A. Isolation and properties of a glycine-rich beta-glycoprotein of human serum. Biochim Biophys Acta. 1970 Dec 22;221(3):529–535. doi: 10.1016/0005-2795(70)90224-2. [DOI] [PubMed] [Google Scholar]
  7. Bokisch V. A., Müller-Eberhard H. J., Cochrane C. G. Isolation of a fragment (C3a) of the third component of human complement containing anaphylatoxin and chemotactic activity and description of an anaphylatoxin inactivator of human serum. J Exp Med. 1969 May 1;129(5):1109–1130. doi: 10.1084/jem.129.5.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Caporale L. H., Gaber S. S., Kell W., Götze O. A fluorescent assay for complement activation. J Immunol. 1981 May;126(5):1963–1965. [PubMed] [Google Scholar]
  9. Clardy C. W., Forristal J., Strife C. F., West C. D. A properdin dependent nephritic factor slowly activating C3, C5, and C9 in membranoproliferative glomerulonephritis, types I and III. Clin Immunol Immunopathol. 1989 Mar;50(3):333–347. doi: 10.1016/0090-1229(89)90141-4. [DOI] [PubMed] [Google Scholar]
  10. Cochrane C. G., Müller-Eberhard H. J., Aikin B. S. Depletion of plasma complement in vivo by a protein of cobra venom: its effect on various immunologic reactions. J Immunol. 1970 Jul;105(1):55–69. [PubMed] [Google Scholar]
  11. Daha M. R., Deelder A. M., Van Es L. A. Stabilization of the amplification convertase of complement by monoclonal antibodies directed against human factor B. J Immunol. 1984 May;132(5):2538–2542. [PubMed] [Google Scholar]
  12. Danner R. L., Elin R. J., Hosseini J. M., Wesley R. A., Reilly J. M., Parillo J. E. Endotoxemia in human septic shock. Chest. 1991 Jan;99(1):169–175. doi: 10.1378/chest.99.1.169. [DOI] [PubMed] [Google Scholar]
  13. Dodds W. J., Pickering R. J. The effect of cobra venom factor on hemostasis in guinea pigs. Blood. 1972 Sep;40(3):400–411. [PubMed] [Google Scholar]
  14. Fearon D. T., Ruddy S., Schur P. H., McCabe W. R. Activation of the properdin pathway of complement in patients with gram-negative of bacteremia. N Engl J Med. 1975 May 1;292(18):937–940. doi: 10.1056/NEJM197505012921802. [DOI] [PubMed] [Google Scholar]
  15. First M. R., Schroeder T. J., Hurtubise P. E., Mansour M. E., Penn I., Munda R., Balistreri W. F., Alexander J. W., Melvin D. B., Fidler J. P. Successful retreatment of allograft rejection with OKT3. Transplantation. 1989 Jan;47(1):88–91. doi: 10.1097/00007890-198901000-00020. [DOI] [PubMed] [Google Scholar]
  16. Galfrè G., Milstein C. Preparation of monoclonal antibodies: strategies and procedures. Methods Enzymol. 1981;73(Pt B):3–46. doi: 10.1016/0076-6879(81)73054-4. [DOI] [PubMed] [Google Scholar]
  17. Glover G. I., Schasteen C. S., Liu W. S., Levine R. P. Synthetic peptide inhibitors of complement serine proteases--I. Identification of functionally equivalent protease inhibitor sequences in serpins and inhibition of C1s and D. Mol Immunol. 1988 Dec;25(12):1261–1267. doi: 10.1016/0161-5890(88)90040-5. [DOI] [PubMed] [Google Scholar]
  18. Goldstein G., Fuccello A. J., Norman D. J., Shield C. F., 3rd, Colvin R. B., Cosimi A. B. OKT3 monoclonal antibody plasma levels during therapy and the subsequent development of host antibodies to OKT3. Transplantation. 1986 Nov;42(5):507–511. doi: 10.1097/00007890-198611000-00013. [DOI] [PubMed] [Google Scholar]
  19. Grossman N., Schmetz M. A., Foulds J., Klima E. N., Jimenez-Lucho V. E., Leive L. L., Joiner K. A., Jiminez V. Lipopolysaccharide size and distribution determine serum resistance in Salmonella montevideo. J Bacteriol. 1987 Feb;169(2):856–863. doi: 10.1128/jb.169.2.856-863.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Guenter C. A., Fiorica V., Hinshaw L. B. Cardiorespiratory and metabolic responses to liver E. coli and endotoxin in the monkey. J Appl Physiol. 1969 Jun;26(6):780–786. doi: 10.1152/jappl.1969.26.6.780. [DOI] [PubMed] [Google Scholar]
  21. Götze O., Müller-Eberhard H. J. The C3-activator system: an alternate pathway of complement activation. J Exp Med. 1971 Sep 1;134(3 Pt 2):90s–108s. [PubMed] [Google Scholar]
  22. Hsueh W., Sun X., Rioja L. N., Gonzalez-Crussi F. The role of the complement system in shock and tissue injury induced by tumour necrosis factor and endotoxin. Immunology. 1990 Jul;70(3):309–314. [PMC free article] [PubMed] [Google Scholar]
  23. Jaffers G. J., Fuller T. C., Cosimi A. B., Russell P. S., Winn H. J., Colvin R. B. Monoclonal antibody therapy. Anti-idiotypic and non-anti-idiotypic antibodies to OKT3 arising despite intense immunosuppression. Transplantation. 1986 May;41(5):572–578. doi: 10.1097/00007890-198605000-00004. [DOI] [PubMed] [Google Scholar]
  24. Joiner K. A., Grossman N., Schmetz M., Leive L. C3 binds preferentially to long-chain lipopolysaccharide during alternative pathway activation by Salmonella montevideo. J Immunol. 1986 Jan;136(2):710–715. [PubMed] [Google Scholar]
  25. Kaneko I., Fearon D. T., Austen K. F. Inhibition of the alternative pathway of human complement in vitro by a natural microbial product, complestatin. J Immunol. 1980 Mar;124(3):1194–1198. [PubMed] [Google Scholar]
  26. Kearney J. F., Radbruch A., Liesegang B., Rajewsky K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979 Oct;123(4):1548–1550. [PubMed] [Google Scholar]
  27. Klein P. G., Wellensiek H. J. Multiple nature of the third component of guinea-pig complement. I. Separation and characterization of three factors a, b, and c, essential for haemolysis. Immunology. 1965 Jun;8(6):590–603. [PMC free article] [PubMed] [Google Scholar]
  28. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  29. McCabe W. R. Serum complement levels in bacteremia due to gram-negative organisms. N Engl J Med. 1973 Jan 4;288(1):21–23. doi: 10.1056/NEJM197301042880105. [DOI] [PubMed] [Google Scholar]
  30. Morrison D. C., Kline L. F. Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides (LPS). J Immunol. 1977 Jan;118(1):362–368. [PubMed] [Google Scholar]
  31. Nuytinck J. K., Goris R. J., Weerts J. G., Schillings P. H., Stekhoven J. H. Acute generalized microvascular injury by activated complement and hypoxia: the basis of the adult respiratory distress syndrome and multiple organ failure? Br J Exp Pathol. 1986 Aug;67(4):537–548. [PMC free article] [PubMed] [Google Scholar]
  32. Pangburn M. K. Analysis of recognition in the alternative pathway of complement. Effect of polysaccharide size. J Immunol. 1989 Apr 15;142(8):2766–2770. [PubMed] [Google Scholar]
  33. Perosa F., Carbone R., Ferrone S., Dammacco F. Purification of human immunoglobulins by sequential precipitation with caprylic acid and ammonium sulphate. J Immunol Methods. 1990 Mar 27;128(1):9–16. doi: 10.1016/0022-1759(90)90458-8. [DOI] [PubMed] [Google Scholar]
  34. Ratkowsky D. A., Reedy T. J. Choosing near-linear parameters in the four-parameter logistic model for radioligand and related assays. Biometrics. 1986 Sep;42(3):575–582. [PubMed] [Google Scholar]
  35. Ross G. D., Medof M. E. Membrane complement receptors specific for bound fragments of C3. Adv Immunol. 1985;37:217–267. doi: 10.1016/s0065-2776(08)60341-7. [DOI] [PubMed] [Google Scholar]
  36. Schasteen C. S., Levine R. P., McLafferty S. A., Finn R. F., Bullock L. D., Mayden J. C., Glover G. I. Synthetic peptide inhibitors of complement serine proteases--III. Significant increase in inhibitor potency provides further support for the functional equivalence hypothesis. Mol Immunol. 1991 Jan-Feb;28(1-2):17–26. doi: 10.1016/0161-5890(91)90082-u. [DOI] [PubMed] [Google Scholar]
  37. Schasteen C. S., McLafferty S. A., Glover G. I., Han C. Y., Mayden J. C., Liu W. S., Levine R. P. Synthetic peptide inhibitors of complement serine proteases--II. Effects on hemolytic activity and production of C3a and C4a. Mol Immunol. 1988 Dec;25(12):1269–1275. doi: 10.1016/0161-5890(88)90041-7. [DOI] [PubMed] [Google Scholar]
  38. Schirmer W. J., Schirmer J. M., Naff G. B., Fry D. E. Systemic complement activation produces hemodynamic changes characteristic of sepsis. Arch Surg. 1988 Mar;123(3):316–321. doi: 10.1001/archsurg.1988.01400270050007. [DOI] [PubMed] [Google Scholar]
  39. Sjöholm A. G., Braconier J. H., Söderström C. Properdin deficiency in a family with fulminant meningococcal infections. Clin Exp Immunol. 1982 Nov;50(2):291–297. [PMC free article] [PubMed] [Google Scholar]
  40. Smedegård G., Cui L. X., Hugli T. E. Endotoxin-induced shock in the rat. A role for C5a. Am J Pathol. 1989 Sep;135(3):489–497. [PMC free article] [PubMed] [Google Scholar]
  41. Suffredini A. F., Fromm R. E., Parker M. M., Brenner M., Kovacs J. A., Wesley R. A., Parrillo J. E. The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med. 1989 Aug 3;321(5):280–287. doi: 10.1056/NEJM198908033210503. [DOI] [PubMed] [Google Scholar]
  42. Takada Y., Arimoto Y., Mineda H., Takada A. Inhibition of the classical and alternative pathways by amino acids and their derivatives. Immunology. 1978 Mar;34(3):509–515. [PMC free article] [PubMed] [Google Scholar]
  43. Tanaka E., Hong K., Kinoshita T., Takata Y., Kozono H., Takeda J., Yoden A., Inoue K. Murine monoclonal anti-Ba antibody that enhances haemolytic activity of factor B. Immunology. 1991 Aug;73(4):383–387. [PMC free article] [PubMed] [Google Scholar]
  44. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Ueda A., Kearney J. F., Roux K. H., Volanakis J. E. Probing functional sites on complement protein B with monoclonal antibodies. Evidence for C3b-binding sites on Ba. J Immunol. 1987 Feb 15;138(4):1143–1149. [PubMed] [Google Scholar]
  46. Vogel C. W., Smith C. A., Müller-Eberhard H. J. Cobra venom factor: structural homology with the third component of human complement. J Immunol. 1984 Dec;133(6):3235–3241. [PubMed] [Google Scholar]
  47. Weisman H. F., Bartow T., Leppo M. K., Marsh H. C., Jr, Carson G. R., Concino M. F., Boyle M. P., Roux K. H., Weisfeldt M. L., Fearon D. T. Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis. Science. 1990 Jul 13;249(4965):146–151. doi: 10.1126/science.2371562. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES