Abstract
The surface of zymosan (Zy), by affording a protected microenvironment for C3b and the amplification convertase stabilized by properdin, P,C3b,Bb, shifts the alternative complement pathway from slow fluid phase turnover to the amplification phase of its expression. This mode of activation is in contradistinction to that of the classical pathway, which follows conversion of a proenzyme, Cl, to its active form, C1. Under conditions in which the control proteins, C3b inactivator (C3bINA) and beta1H, completely, inactivated C3b on the sheep erythrocyte intermediate, EAC4b,3b, the activity of C3b bound to Zy,ZyC3b, was diminished by only one-third. Further, when ZyC3b was converted to ZyC3b,Bb,P there was an additional point of deregulation in that the convertase was resistant to beta1H-mediated decay-dissociation while P,C3b,Bb on the sheep erythrocyte exhibited the usual susceptibility to beta1H. That Zy alone could indeed promote rapid C3 cleavage by the alternative pathway through assembly and protection of the amplification convertase on its surface was demonstrated with a mixture of alternative pathway proteins, C3,B,D,P, C3bINA, and beta1H, that had each been purified to homogeneity. Interaction of these proteins at one-tenth their relative serum concentrations with Zy permitted low-grade inactivation of C3 and B to advance to the level of amplification after a 15 min lag period. Because the reaction of the purified proteins proceeded spontaneously when either regulatory protein was deleted, the effect of Zy was attributed to deregulation rather than to conversion of one of the proteins to a specific initiating state. The alternative pathway, through the normal presence of D, interacts with a microbial surface, such as Zy, to amplify deposition of C3b by circumvention of endogenous regulatory mechanisms, thereby augmenting host defense.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alper C. A., Goodkofsky I., Lepow I. H. The relationship of glycine-rich -glycoprotein to factor B in the properdin system and to the cobra factor-binding protein of huan serum. J Exp Med. 1973 Feb 1;137(2):424–437. doi: 10.1084/jem.137.2.424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alper C. A., Rosen F. S., Lachmann P. J. Inactivator of the third component of complement as an inhibitor in the properdin pathway. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2910–2913. doi: 10.1073/pnas.69.10.2910. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Daha M. R., Fearon D. T., Austen K. F. Isolation of alternative pathway C3 convertase containing uncleaved B and formed in the presence of C3 nephritic factor (C3neF). J Immunol. 1976 Feb;116(2):568–570. [PubMed] [Google Scholar]
- Ensky J., Hinz C. F., Jr, Todd E. W., Wedgwood R. J., Boyer J. T., Lepow I. H. Properties of highly purified human properdin. J Immunol. 1968 Jan;100(1):142–158. [PubMed] [Google Scholar]
- Fearon D. T., Austen K. F. Initiation of C3 cleavage in the alternative complement pathway. J Immunol. 1975 Nov;115(5):1357–1361. [PubMed] [Google Scholar]
- Fearon D. T., Austen K. F. Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase. J Exp Med. 1975 Oct 1;142(4):856–863. doi: 10.1084/jem.142.4.856. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fearon D. T., Austen K. F. Properdin: initiation of alternative complement pathway. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3220–3224. doi: 10.1073/pnas.72.8.3220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fearon D. T., Austen K. F., Ruddy S. Formation of a hemolytically active cellular intermediate by the interaction between properdin factors B and D and the activated third component of complement. J Exp Med. 1973 Dec 1;138(6):1305–1313. doi: 10.1084/jem.138.6.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fearon D. T., Austen K. F., Ruddy S. Properdin factor D. II. Activation to D by properdin. J Exp Med. 1974 Aug 1;140(2):426–436. doi: 10.1084/jem.140.2.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fearon D. T., Austen K. F., Ruddy S. Properdin factor D: characterization of its active site and isolation of the precursor form. J Exp Med. 1974 Feb 1;139(2):355–366. doi: 10.1084/jem.139.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gigli I., Nelson R. A., Jr Complement dependent immune phagocytosis. I. Requirements for C'1, C'4, C'2, C'3. Exp Cell Res. 1968 Jul;51(1):45–67. doi: 10.1016/0014-4827(68)90158-4. [DOI] [PubMed] [Google Scholar]
- 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]
- Hunsicker L. G., Ruddy S., Austen K. F. Alternate complement pathway: factors involved in cobra venom factor (CoVF) activation of the third component of complement (C3). J Immunol. 1973 Jan;110(1):128–138. [PubMed] [Google Scholar]
- Kolb W. P., Müller-Eberhard H. J. The membrane attack mechanism of complement. Verification of a stable C5-9 complex in free solution. J Exp Med. 1973 Aug 1;138(2):438–451. doi: 10.1084/jem.138.2.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LEPOW I. H., NAFF G. B., TODD E. W., PENSKY J., HINZ C. F. Chromatographic resolution of the first component of human complement into three activities. J Exp Med. 1963 Jun 1;117:983–1008. doi: 10.1084/jem.117.6.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lynen R., Vogt W., Schmidt G., Dieminger L. Purification of a human serum protein ("factor E") which enhances cobra venom factor-induced indirect lysis. Identification with the fifth component of complement. Z Immunitatsforsch Exp Klin Immunol. 1976 Apr;151(2):105–116. [PubMed] [Google Scholar]
- Minta J. O., Lepow I. H. Studies on the sub-unit structure of human properdin. Immunochemistry. 1974 Jul;11(7):361–368. doi: 10.1016/0019-2791(74)90189-x. [DOI] [PubMed] [Google Scholar]
- Müller-Eberhard H. J., Götze O. C3 proactivator convertase and its mode of action. J Exp Med. 1972 Apr 1;135(4):1003–1008. doi: 10.1084/jem.135.4.1003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller-Eberhard H. J., Polley M. J., Calcott M. A. Formation and functional significance of a molecular complex derived from the second and the fourth component of human complement. J Exp Med. 1967 Feb 1;125(2):359–380. doi: 10.1084/jem.125.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nelson R. A., Jr, Jensen J., Gigli I., Tamura N. Methods for the separation, purification and measurement of nine components of hemolytic complement in guinea-pig serum. Immunochemistry. 1966 Mar;3(2):111–135. doi: 10.1016/0019-2791(66)90292-8. [DOI] [PubMed] [Google Scholar]
- Nicol P. A., Lachmann P. J. The alternate pathway of complement activation. The role of C3 and its inactivator (KAF). Immunology. 1973 Feb;24(2):259–275. [PMC free article] [PubMed] [Google Scholar]
- Nilsson U. R., Mandle R. J., Jr, McConnell-Mapes J. A. Human C3 and C5: subunit structure and modifications by trypsin and C42-C423. J Immunol. 1975 Feb;114(2 Pt 2):815–822. [PubMed] [Google Scholar]
- PILLEMER L., BLUM L., LEPOW I. H., ROSS O. A., TODD E. W., WARDLAW A. C. The properdin system and immunity. I. Demonstration and isolation of a new serum protein, properdin, and its role in immune phenomena. Science. 1954 Aug 20;120(3112):279–285. doi: 10.1126/science.120.3112.279. [DOI] [PubMed] [Google Scholar]
- Ruddy S., Austen K. F. C3 inactivator of man. I. Hemolytic measurement by the inactivation of cell-bound C3. J Immunol. 1969 Mar;102(3):533–543. [PubMed] [Google Scholar]
- Ruddy S., Austen K. F. C3b inactivator of man. II. Fragments produced by C3b inactivator cleavage of cell-bound or fluid phase C3b. J Immunol. 1971 Sep;107(3):742–750. [PubMed] [Google Scholar]
- Schreiber R. D., Götze O., Müller-Eberhard H. J. Alternative pathway of complement: demonstration and characterization of initiating factor and its properdin-independent function. J Exp Med. 1976 Oct 1;144(4):1062–1075. doi: 10.1084/jem.144.4.1062. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spitzer R. E., Vallota E. H., Forristal J., Sudora E., Stitzel A., Davis N. C., West C. D. Serum C'3 lytic system in patients with glomerulonephritis. Science. 1969 Apr 25;164(3878):436–437. doi: 10.1126/science.164.3878.436. [DOI] [PubMed] [Google Scholar]
- Thorell J. I., Larsson I. Lactoperoxidase coupled to polyacrylamide for radio-iodination of proteins to high specific activity. Immunochemistry. 1974 Apr;11(4):203–206. doi: 10.1016/0019-2791(74)90329-2. [DOI] [PubMed] [Google Scholar]
- Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
- Weiler J. M., Daha M. R., Austen K. F., Fearon D. T. Control of the amplification convertase of complement by the plasma protein beta1H. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3268–3272. doi: 10.1073/pnas.73.9.3268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whaley K., Ruddy S. Modulation of the alternative complement pathways by beta 1 H globulin. J Exp Med. 1976 Nov 2;144(5):1147–1163. doi: 10.1084/jem.144.5.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]