SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
This article summarized the physicohemical data on the factors which compose the properdin system in guinea pig and man. The following other topics are discussed: (1) Activation of the properdin system; (2) Formation of the initiating and amplification C3 convertases; (3) Formation of the C5 convertase, and (4) Regulatory control mechanisms of the properdin system.
Persistent activation of the complement system after escape from control by the regulatory proteins results in an excessive release of split products with inflammatory properties. Serum levels of the regulatory proteins of the complement system (Cl-INH, H, I and AT III) were assayed by the radial immunodiffusion technique in 521 serum samples from 124 patients with idiopathic chronic glomerulonephritis divided into two groups: 81 cases with normal renal function (NRF), and 43 cases with deteriorated renal function (DRF). Significant high mean levels of Cl-INH, H, I and AT III were found in patients with NRF, when they were compared with DRF patient groups. Positive correlations between the regulatory proteins and the corresponding complement components were found in patients with NRF, whereas they were reduced considerably in patients with DRF. Serial measurement of the control proteins showed a decay of the levels of Cl-INH, H and I in patients with progressive impairment of renal function. The presence of high levels of regulatory proteins suggest that a control mechanism may occur in patients with NRF; measurement of these proteins could, therefore, be of prognostic value, as the presence of high levels are indicative of a block of the complement system.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Activation of complement via the alternative pathway represents one means of natural resistance to infection because it is capable of neutralizing a wide variety of potential pathogens in the total absence of antibody. The pathway involves six serum proteins and possesses a unique amplification system capable of depositing large numbers of C3b molecules on the surfaces of activating particles. C3b deposition enhances phagocytosis and results in activation of the membrane attack pathway of complement. C3b attachment is covalent, arising from a reaction between an intramolecular thiolester bond in nascent C3b and nucleophiles such as hydroxyl groups on surface carbohydrates. The reactions that initiate C3b attachment are not specific interactions like those initiating other biological cascade systems, but involve slow, spontaneous hydrolysis of the thiolester bond in C3 and subsequent random deposition of C3b onto all nearby surfaces. Once bound, C3b is capable of discriminating between host-derived cells and activating particles. Recognition is evidenced by a lower affinity between activator-bound C3b and the complement control protein factor H. Measurements of the association constant between unbound, soluble C3b and factor H suggest that activator-bound C3b recognizes structures on activators that inhibit factor H binding.
Examination of C3b deposition on the surface of activators during alternative pathway activation revealed three temporal phases: a lag phase, an amplification phase, and a heretofore uncharacterized plateau phase. During the plateau phase no C3b deposition appeared to occur even in the presence of an excess of alternative pathway components. Double label experiments, however, revealed that the plateau was a steady state between continued C3b deposition and release of C3b or C3bi from the activator. Under conditions of excess complement it was found that deposition of increasing numbers of C3b molecules caused a gradual increase in the ability of Factors H and I to inactivate newly deposited C3b; i.e., the deposited C3b converted the activator into a nonactivator. The data indicate that the surface of rabbit erythrocytes is rendered completely nonactivating when 2.4 X 10(6) molecules of C3b plus C3bi are bound per cell. The plateau of C3b deposition appears to represent the maximum steady state level maintainable by a given concentration of complement components, and it also reflects conversion of an activating surface to one resembling a nonactivator.
Explore the source record for details and available documents.
beta 1Hrat was purified to homogeneity from fresh rat plasma by precipitation with 28.6% ammonium sulfate followed by sequential chromatography on DEAE-Sephacel, Biorex-70, and gel filtration on Sephacryl-S300. The final material was homogeneous on SDS-PAGE analysis and had an apparent m.w. of 150,000. Reduction with dithiothreitol did not affect its m.w., suggesting that the molecule is composed of one polypeptide chain. The recovery of beta 1H was approximately 10%. A monospecific antibody against beta 1Hrat was obtained from immunized rabbits, which recognized beta 1Hrat as a protein with beta-electrophoretic mobility upon immunoelectrophoresis of fresh rat plasma. The concentration of beta 1H in plasma of normal 4-mo-old Wistar rats was 243.5 +/- 36.3 micrograms/ml (mean +/- S.D.). beta 1Hrat in this study was detected by its capacity to inhibit formation of the P-stabilized cell-bound amplification C3/C5 convertase composed of cell-bound C3bhu and Bbhu. Purified beta 1Hrat produced a dose-related, first-order loss of convertase function and release of 126I-Bbhu from the P-stabilized C3bhuBbhu convertase, indicating a mechanism of action by decay-dissociation of Bbhu from the complex C3bhuBbhuP. beta 1Hrat was at least four times less effective than beta 1Hhu in release of 125I-Bbhu from the homologous convertase composed of C3bhu and Bbhu. On the other hand beta 1H was twice as effective in releasing 125I-Bbrat from the convertase composed of C3bratBbratP when compared to beta 1Hhu. These differences are presumably dependent upon the species-specific affinity of beta 1H from humans or rats for C3bhu or C3brat, respectively.
The effect of the synthetic glucocorticoid dexamethasone (DXM) on the secretion by human monocytes of alternative complement proteins C3, factor B and factor H was investigated. Results indicated that DXM modulates this secretion in a direction which would be consistent with its anti-inflammatory properties. DXM, at therapeutic concentrations, had a suppressive effect on C3 and factor B secretion and a stimulatory effect on factor H secretion by monocytes. This differential modulation on C3, factor B and factor H secretion was similar in mature macrophages. Together with previous studies showing that DXM had a suppressive effect on C3 and factor B secretion and a stimulatory effect on factor H secretion by human endothelial cells, our results indicate that DXM appears to have the general property of regulating local production of complement components so as to control complement activation.
A simple method for isolation from human serum of the complement alternative pathway factor B, in a yield over 40% and purity over 80% with respect to protein, has been developed. Such a high yield was reached due to rejection of ammonium sulphate fractionation and employment of only two chromatographic stages: on CM-Sephadex C-50 and on DEAE-Sepharose CL-6B. An additional chromatography on QAE-Sephadex A-50 provides factor B of 100% purity but with a loss of some amount of protein (yield approximately 20%). One of the fractions, obtained at the first stage of factor B purification, contained also factor D. After rechromatography on CM-Sephadex C-50 and gel filtration on Sephadex G-75 it afforded factor D in yield more than 60% and purity above 100%.
Short-term cultures of human peripheral blood monocytes were shown to synthesize the alternative pathway complement components C3, factors B (B) and D (D), and properdin, the regulatory proteins C3b inactivator (C3bINA) and beta 1H, in addition to C2, C4, and C5. B, D, properdin, C3bINA, and C2 were detected by functional assays, whereas beta 1H, C4, C3, and C5 could only be detected using immunochemical procedures. Immunoperoxidase localization studies showed that all the cells in each culture contained each component, so it is possible that all monocytes synthesize each component. It is concluded that cells of the monocyte-macrophage series form a mobile source of complement components and regulatory proteins which can be concentrated at sites of inflammation.
The addition of 5-10% of fresh normal human serum (NHS) from normal individuals into a culture of primarily HIV-1-infected CD4+ leukemic T-cell lines CEM and MT4 was found to rescue the infected cells from cytopathic death, enabling the cells to achieve growth within 10 days. The HIV-1-infected cells cultured in ordinary medium with fetal calf serum (FCS) all died within 10 days. The effect of NHS was ascribed to human complement component factor B and one or more factor B-dependent heat-labile co-factors. The cells which survived in the presence of NHS rapidly lost surface expression of CD4 and became completely resistant to rechallenge by HIV-1. Viral genomes were dramatically reduced in surviving cells within 30 days, and one cell-line CEM completely expelled them during this period. The results suggest that factor B has protective and potential therapeutic significance in HIV-1 infection.
The carbohydrate composition of the second, third and fifth components of human complement (C2, C3 and C5) and of factors B and D was determined employing gas-chromatographic and mass-spectrometric methods. C2 was found to contain 15.9% carbohydrate composed of fucose, galactose, mannose, N-acetylglucosamine and N-acetylneuraminate (approximate molar ratio 1:4:9:9:4). N-acetylglucosamine and mannose (approximate molar ratio 1:4), amounting to 1.7% of the mass of the molecule, were the only monosaccharides detected in C3. C5 contained 3.8% carbohydrate composed of galactose, mannose, N-acetylglucosamine and N-acetylneuraminate (approximate molar ratio 2:4:4-5:2). The carbohydrate moiety of B consisted of fucose, galactose, mannose, N-acetylglucosamine and N-acetylneuraminate (molar ratio 1:2:3:4:2). The total carbohydrate content of B was estimated at 8.6%. In addition to these monosaccharides, glucose (0.4-0.9%) was also detected in all preparations analysed. Glucose was the only sugar detected in D.
Human interleukin (IL) 6 is a multifunctional cytokine which is synthesized by fibroblasts in response to many stimuli, including bacterial lipopolysaccharide (LPS). During acute-phase response, liver cells secrete a specific group of proteins among which components of the complement system and IL 6 appear to be an important mediator of this response. Human skin fibroblasts also synthesize at least seven proteins of the complement system. Each of these seems to be characteristically regulated by soluble mediators of the inflammatory process. Here we report that in fibroblasts, IL 6 induces increases in the rate of synthesis of factor B and C3, activator proteins of the alternative pathway of complement activation. The increases in factor B and C3 were concentration dependent reaching about 40- and 15-fold, respectively. The protein increases were observed within 4 h after IL 6 addition to the cells and were accompanied by increase in factor B and C3 mRNA. The data suggest that the induction of factor B and C3 by LPS may be mediated, at least in part, by IL 6 induced by LPS. This new function of IL 6 could provide a local protection against invading agents through activation of the antibody-independent alternative pathway of complement activation.