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PubMed1995

A component of the medicinal herb ephedra blocks activation in the classical and alternative pathways of complement.

Extracts of the herb Ephedra sinica have long been used in traditional Chinese medicine for the treatment of, among other conditions, acute nephritis. In preliminary studies it was shown that extracts of ephedra caused inhibition of complement in vitro. We thus set out to isolate the active component(s) of this herb, to examine the complement-inhibiting capacity in sera from different species, and to characterize the mechanism(s) by which it inhibits complement. Aqueous extraction of the herb followed by fractionation using thin layer chromatography (TLC) demonstrated that complement-inhibiting activity resided within a single band, hereafter termed the complement-inhibiting component (CIC), which represents an as yet uncharacterized polyanionic carbohydrate molecule. TLC-purified CIC inhibited the classical complement pathway in all species tested (human, pig, guinea pig, rat and rabbit). Using erythrocyte intermediates and sera specifically depleted of individual components it was apparent that CIC inhibited C2. This finding was confirmed using purified human C2, CIC causing a dose-dependent loss of C2 haemolytic activity. At much higher doses, CIC also showed some inhibiting effect in the terminal pathway, and this was shown to be due to inhibition of C9. In the alternative pathway CIC also showed inhibitory activity, although its site of action in this pathway remains unresolved. In Chinese medicine the herb is taken orally, though no studies of complement levels in patients taking the herb have been reported. Preliminary data indicate that oral administration in rats causes a partial inhibition of serum complement activity. Given the current enthusiasm for complement inhibition as a therapy for inflammatory diseases, this non-toxic, naturally occurring agent might be of therapeutic value.

Animals↗
PubMed1983

Serial complement measurements in patients with leukaemia.

Haemolytic activity of the classical and alternative pathways and the levels of C4, C3 and factor B were serially measured in 153 serum samples of 41 patients with different types of leukaemia (9 AML, 14 ALL, 10 CML and 8 CLL). In parallel, the concentration of circulating immune complexes (CIC) was estimated using two methods, the complement consumption assay and the Clq-solubility test. Different complement profiles were found in different types of leukaemia. In AML, each complement parameter tested was elevated as compared to the control values (sera of healthy blood donors). Similar results were observed in ALL, although the differences were less marked. In CML, dissociation of the classical and alternative pathway activities was found: activities of the classical pathway and C4 were significantly elevated, whereas activity of the alternative pathway as well as C3 and factor B concentration did not differ significantly from the control values. In CLL, normal or slightly depressed complement levels were found. The concentration of circulating immune complexes measured by both methods was significantly increased as compared to control values. No significant positive or negative correlations were found between the complement levels and the immune complex concentrations determined in the same sera. An association between the clinical course of acute leukaemia and the complement levels was observed: significantly elevated complement titres were found in the blastic stage of the disease, whereas in remission normal values were recorded. The results of complement measurements performed in serum samples obtained before and after combination chemotherapy were compared on 32 occasions. In parallel to a significant decrease in the absolute number of blast cells in the peripheral blood, a normalization of the increased complement levels was observed after treatment.

Acute Disease↗
PubMed1996

Effect of amplification of the Cap b locus on complement-mediated bacteriolysis and opsonization of type b Haemophilus influenzae.

Amplification of the Cap b locus of Haemophilus influenzae occurs frequently in clinical isolates and has been proposed to be a mechanism by which this organism evades host defense. To determine if amplification of this locus affected complement fixation, in vitro studies to determine complement-mediated bacteriolysis and complement-mediated opsonization of an isogenic set of organisms containing 2, 3, and 4 copies of the Cap b locus were performed. Organisms containing 4 copies of the Cap b locus were significantly more resistant to antibody-dependent, classical complement pathway-directed bacteriolysis than were organisms containing 2 copies. Organisms containing 3 copies of this locus exhibited intermediate susceptibility to lysis. Complement-mediated opsonization of these organisms was assessed by determining the degree of binding of bacteria to murine or human macrophages or to nonphagocytic cells transfected with the genes for human Mac-1, the complement receptor type 3. In all three assay systems, organisms containing 4 copies of the Cap b locus bound less well than did organisms containing 2 copies of this locus. Consistent with their decreased susceptibility to lysis and opsonization, organisms with 4 copies of the Cap b locus fixed less C3 than did organisms containing 2 copies. These data demonstrate that amplification of the Cap b locus is associated with decreased susceptibility to complement-mediated lysis and decreased complement-mediated opsonization and suggest that amplification is used by these pathogens to increase their resistance to complement-dependent host defense mechanisms [correction of mecanisms].

Adult↗
PubMed1993

Complement-mediated binding of naturally glycosylated and glycosylation-modified human immunodeficiency virus type 1 to human CR2 (CD21).

Particulate glycoproteins lacking sialic acid, such as desialylated enveloped viruses, readily activate complement through the alternative pathway. Human immunodeficiency virus type 1 (HIV-1) contains two heavily glycosylated and partially sialylated envelope glycoproteins: a surface gp120 and a transmembrane gp41. The abilities of naturally glycosylated HIV-1 and glycosylation-modified HIV-1 to interact with the complement system were examined with a biological assay which measured the binding of whole virus particles to cells expressing CR2 (CD21), the complement receptor found naturally in abundance on follicular dendritic cells and immature B cells. HIV-1 IIIB was synthesized in the presence or absence of the mannosidase II inhibitor, swainsonine, to give rise to high-mannose-type, nonsialylated, nonfucosylated carbohydrate moieties. The virus also was treated with neuraminidase or endo-beta-galactosidase to remove terminal sialic acids. An enzyme immunoassay specific for HIV-1 p24 core protein was used to quantitate the amount of virus bound to cell surfaces. Virus particles incubated with 1:3-diluted, fresh HIV-1-negative human serum as a source of complement readily bound to MT-2 (CD4+ CR2+) and Raji-3 (CD4- CR2+) cells but not to CEM (CD4+ CR2-) cells, suggesting that the virus bound to CR2 independently of CD4. Compared with heat-inactivated or C3-deficient sera, fresh complement increased binding by as much as 62 times for naturally glycosylated virus, and 5 times more than this for glycosylation-modified virus. Similar observations were made with freshly isolated, non-mitogen-stimulated peripheral blood mononuclear cells. Additional evidence that HIV-1 bound to CR2 independently of CD4 was provided by the fact that binding was blocked by monoclonal antibody OKB7 (anti-CR2) but not by OKT4a (anti-CD4). Also, the virus bound to transfected K562 cells (CD4-) which expressed recombinant human CR2 but did not bind to untransfected K562 cells. Results obtained with complement component-deficient sera indicated that binding required the alternative complement pathway. Raji-3 and transfected K562 cells could not be infected with HIV-1 in the presence of complement, suggesting that utilization of CR2 as a receptor in the absence of CD4 does not allow virus entry. The demonstration of CR2 as a receptor for HIV-1 in the presence of complement, together with the ability to enhance binding by desialylation, provides new insights into mechanisms of HIV-1-induced immunity and immunopathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Abrupt complement activation and transient neutropenia in patients with acute myocardial infarction treated with streptokinase.

BACKGROUND: Whether and to what extent complement is activated in acute myocardial infarction (AMI) and how it contributes to inflammation of the ischemic area are not yet clear. Fibrinolytic agents used for thrombolysis are known to activate complement in vitro and may contribute to its activation in vivo. The aim of this study was to measure the extent of complement activation in AMI patients, some treated and some not treated with streptokinase. In addition, because abrupt complement activation in vivo is usually associated with leukocyte margination, plugging of cells in the microcirculation, and hypotension, we correlated complement activation with leukocyte numbers and mean arterial pressure. METHODS AND RESULTS: Forty AMI patients were studied: 20 were treated with streptokinase (1.5 million IU IV over 60 minutes), and 20 were not given any fibrinolytic agent. The extent and severity of AMI were not significantly different in both groups. Blood samples were drawn on arrival at the hospital, during streptokinase infusion, and then daily for 1 week. Time-matched samples were also drawn from patients not treated with streptokinase. We measured plasma levels of anaphylatoxin C4a, C3a, and C5a by radioimmunoassay and membrane attack complexes SC5b-9 by enzyme immunoassay. Leukocytes and arterial pressure also were measured when samples were obtained. C4a, C3a, and SC5b-9 levels increased about 10-fold (P < .0001) during infusion of streptokinase. There were no significant increases in complement catabolic products in AMI patients not treated with streptokinase. There was a significant transient leukopenia (mean +/- SEM, -29.5 +/- 7.0%; P = .001) and decreases in systolic and diastolic pressures (systolic, -29.3 +/- 3.2%, P < .0001; diastolic, -27.5 +/- 3.4%, P < .0001) after 15 minutes of streptokinase infusion in coincidence with the peak of anaphylatoxins in plasma. CONCLUSIONS: Streptokinase treatment of AMI causes abrupt activation of the complement system, whereas no significant complement activation can be detected in plasma of AMI patients not treated with fibrinolytic agents. Complement activation causes a transient leukopenia, as reported for such other clinical conditions as dialysis and cardiopulmonary bypass, and possibly contributes to the hypotension observed during streptokinase treatment.

Aged↗
PubMed1988

Complement fixation by pemphigus antibody. V. Assembly of the membrane attack complex on cultured human keratinocytes.

Previous studies have shown that pemphigus vulgaris (PV) IgG will fix early complement components (C1q, C4, and C3) to cultured murine epidermal cell surfaces and that PV IgG and complement alter epidermal cell membrane integrity. The present study was undertaken to determine if assembly of terminal complement components (C5, C6, C7, C8, and C9) and expression of C5b-9 neoantigens occur when PV IgG interacts with human keratinocyte (HuK) cell surface antigens in the presence of a source of complement. Monoclonal antibodies specific for C5, C6, C7, C8, C9, and C5b-9 neoantigens were screened for reactivity to the individual complement components in an assembled complex of human C5b-9 on rabbit red blood cell ghosts. Monoclonal antibodies (tissue culture supernatants) that bound to antigenic determinants accessible in the C5b-9 complex were selected for this study using immunofluorescence methods. HuK treated with PV IgG fixed C5, C6, C7, C8, C9, and C5b-9 neoantigens in a characteristic speckled pattern, while normal IgG did not. Heat inactivation or EDTA treatment of the complement source, or substitution of C2-depleted serum abolished C5, C6, C7, C8, C9, and C5b-9 neoantigen staining. PV IgG and complement also resulted in significant cytotoxicity to cell membranes as assessed using an ethidium bromide-fluorescein diacetate assay. These results suggest that PV IgG will activate the membrane attack complex of the complement system on HuK cell surfaces, resulting in cytotoxicity to cell membranes, further implicating complement in the pathogenesis of pemphigus.

Autoantigens↗
PubMed2006

Deposition of complement proteins on cells treated by photodynamic therapy in vitro.

Activation of the complement system has emerged as a critical event in the response of tumors to photodynamic therapy (PDT) due to its involvement in the vascular effects as well as in the inflammatory and immune reactions observed with this treatment modality. However, the exact mechanism of PDT-induced complement activation has not been precisely characterized. The present study examines the potential of PDT at the cellular level to directly activate the complement system. Mouse tumor SCCVII cells treated by Photofrin-based PDT and post-incubated in the presence of homologous (mouse) serum were analyzed by flow cytometry for binding of complement proteins on their surface. The results show that PDT induced the fixation of complement C3 protein, probably in the form of its activated fragments, and of the terminal membrane attacks complex of complement on the treated SCCVII cells. Deposition of C3/C3 fragments on human umbilical vein endothelial cells (HUVEC) treated by Photofrin-PDT and post-incubated in the presence of human serum was also detected. Complement fixation was preferentially elevated on SCCVII cell undergoing PDT-induced apoptosis. The induction of surface expression of heat shock protein 70 (HSP70) on PDT-treated cells also triggered complement deposition, since the presence of anti-HSP70 antibodies during the post-PDT incubation blocked the anchoring of C3/C3 fragments to SCCVII cells. The fact that PDT-treated cells are recognized by the complement system as their target adds an important element for understanding the mechanism of tumor response to PDT.

Animals↗
PubMed2002

Complement receptors in HIV infection.

Similar to other pathogens, HIV can directly activate the complement pathway even in the absence of antibodies. During and after seroconversion, HIV-specific antibodies enhance the activation of complement and increase deposition of complement fragments on virions dramatically. However, even in the presence of HIV-specific antibodies, no or only poor lysis occurs. HIV has adapted different protection mechanisms to keep complement activation under the threshold necessary to induce virolysis. In addition to its own envelope proteins, the viral envelope contains membrane-anchored host molecules. Among those are complement regulatory proteins that remain functionally active on the surface of HIV and turn down the complement cascade. In addition, serum proteins with complement regulatory activities become secondarily attached onto the virus, thereby enhancing the protection of HIV against complement-mediated damage. Therefore, opsonised virions accumulate in HIV-infected individuals, which subsequently interact with complement receptor (CR) expressing cells. This review is mainly focused on these interactions, which result either in infection of CR-positive cells with high efficiency, or retention of viral particles on their surface via CRs, thereby promoting transmission of virus to other permissive cells.

Animals↗
PubMed2000

Complement activation in the brain after experimental intracerebral hemorrhage.

OBJECT: Brain edema formation following intracerebral hemorrhage (ICH) appears to be partly related to erythrocyte lysis and hemoglobin release. Erythrocyte lysis may be mediated by the complement cascade, which then triggers parenchymal injury. In this study the authors examine whether the complement cascade is activated after ICH and whether inhibition of complement attenuates brain edema around the hematoma. METHODS: This study was divided into three parts. In the first part, 100 microl of autologous blood was infused into the rats' right basal ganglia, and the animals were killed at 24 and 72 hours after intracerebral infusion. Their brains were tested for complement factors C9, C3d, and clusterin (a naturally occurring complement inhibitor) by using immunohistochemical analysis. In the second part of the study, the rats were killed at 24 or 72 hours after injection of 100 microl of blood. The C9 and clusterin proteins were quantitated using Western blot analysis. In the third part, the rats received either 100 microl of blood or 100 microl of blood plus 10 microg of N-acetylheparin (a complement activation inhibitor). Then they were killed 24 or 72 hours later for measurement of brain water and ion contents. It was demonstrated on Western blot analysis that there had been a sixfold increase in C9 around the hematoma 24 hours after the infusion of 100 microl of autologous blood. Marked perihematomal C9 immunoreactivity was detected at 72 hours. Clusterin also increased after ICH and was expressed in neurons 72 hours later. The addition of N-acetylheparin significantly reduced brain edema formation in the ipsilateral basal ganglia at 24 hours (78.5 +/- 0.5% compared with 81.6 +/- 0.8% in control animals, p < 0.001) and at 72 hours (80.9 +/- 2.2% compared with 83.6 +/- 0.9% in control animals, p < 0.05) after ICH. CONCLUSIONS: It was found that ICH causes complement activation in the brain. Activation of complement and the formation of membrane attack complex contributes to brain edema formation after ICH. Blocking the complement cascade could be an important step in the therapy for ICH.

Animals↗
PubMed1991

Complement-dependent antibody-mediated cytotoxicity (C'AMC) to pancreatic islet cells in the spontaneously diabetic BB/OK rat: interference from cell-bound and soluble inhibitors.

Sera from 30 newly diagnosed diabetic BB/OK rats were analyzed cross-sectionally for complement-dependent antibody-mediated cytotoxicity (C'AMC) to pancreatic islet cells using different 51Cr release test systems. The sera contained enough active complement to lyse either sheep erythrocytes or 51Cr-labelled rat islet cells that had been sensitized with specific rabbit antibodies, but, in the presence of BB/OK rat islet cell antibody they released significant amounts of islet cell-bound 51Cr only after addition of rabbit complement. In a one-step assay, 19 out of the 30 sera produced lysis significantly above that by sera from the non-diabetes-prone WOK strain. This was increased 2.5-fold (p less than 0.01) by briefly washing the serum-treated cells before adding complement (two-step assay), indicating that C'AMC inhibitory activity was present in the diabetic sera. Some inhibitory activity could still be detected in heated sera but only when they were added to the cells immediately before the rabbit complement. Islet cell lysis was still substantial after preferential inactivation of factor B of the alternative complement activation pathway (by heating at 50 degrees C), and thus mainly depended on the classical pathway. From these findings it is concluded that (a) islet cell surface antibodies in diabetic rats activate heterologous complement via the classical pathway, (b) anti-islet C'AMC is sensitive both to species-restricted interference in interactions between homologous antibody and homologous complement in the target cell membrane, and to a distinct serum inhibitor that impairs the ability of membrane-fixed BB/OK rat antibody to interact with rabbit complement.

Animals↗
PubMed1991

Inhibition of complement activity in murine leprosy.

NIH mice infected with Mycobacterium lepraemurium (MLM) show a marked depression in their levels of hemolytic complement that is proportional to the degree of infection. The defect affects more the activation of complement through the classical pathway (CPW) than the activation of complement through the alternative pathway. Although this low activity of CPW-complement may be due to different causes (complement consumption by the infecting microorganism, lack of biosynthesis of complement components, or the presence of complement inhibitory factors), our results seem to support the last possibility. The generation of factors in the infected animals that inhibit the autologous activity of complement as the infection goes on reduces the risk of complement-mediated tissue damage and prolongs the survival time of the host, a wise strategy on the part of the MLM to assure its own survival as a parasite.

Animals↗
PubMed1989

Antibody complement-dependent bacteriolysis in experimentally induced pasteurellosis in mice.

Affinity-purified bovine immunoglobulin isotypes were bacteriolytic for Pasteurella haemolytica biotype A, serotype 1 (PHA-1). This bacteriolysis was specific and complement-dependent. The IgM and IgG1 were the most active isotypes in the classic complement cascade. These isotypes also induced bacteriolysis through the alternative complement cascade. The comparative bacteriolytic activities of IgG1 and IgM were equal within each cascade; however, the bacteriolytic activities of IgG1 and IgM were lower in the alternative cascade than in the classical cascade. The IgG2 was more bacteriolytic than IgA in the classic and alternative complement pathways. Bovine immunoglobulins passively protected C57BL/6 mice from experimentally induced pasteurellosis. There were no major differences in the protection among hyperimmune sera, purified IgM, or purified IgG. Mice were protected from PHA-1 by approximately 1.9 micrograms of IgG and 1.2 or 0.1 micrograms of IgM. Elimination of murine complement with cobra venom factor 3 reduced PHA-1 clearance in passively immunized C57BL/6 mice. The protective effect of IgM mediated resistance was highly dependent on an intact complement system. The intact complement cascade was associated with enhanced clearance of PHA-1 from the liver. Although PHA-1 was susceptible to antibody complement-mediated bacteriolysis in vitro, the dependence on an intact complement cascade was not absolute in experimentally induced murine septicemic pasteurellosis.

Animals↗
PubMed1989

Complement-mediated enhancement of IgA-induced H2O2 release by human polymorphonuclear leucocytes.

In a previous study we have demonstrated that heat-killed Staphylococcus aureus opsonized with either purified human serum IgA or secretory IgA (sIgA) can induce a respiratory burst (measured as H2O2 release) in human polymorphonuclear leucocytes (PMN; Gorter et al., 1987). In the present study we have investigated whether opsonization of IgA-coated staphylococci with complement has an additional effect on the H2O2 release of PMN. It was demonstrated that staphylococci coated with IgA (or sIgA) and subsequently opsonized with complement induced at least a two-fold increase in the specific H2O2 release compared with bacteria coated with IgA (or sIgA) alone (P less than 0.05 and P less than 0.02, respectively). The co-operative effect of IgA and complement was also observed in the presence of 10 mM ethyleneglycoltetraacetic acid containing 5 mM MgCl2 (MgEGTA), suggesting that activation of the alternative pathway of complement is sufficient to exert this effect. Using D-deficient serum as a source of complement we could demonstrate that activation of the alternative pathway is essential for the co-operative effect of complement and IgA. The increase in specific H2O2 release caused by complement was found to be dependent on the amount of IgA initially used to opsonize the bacteria. Finally the co-operative effect of IgA and complement was not restricted to one IgA subclass, because an additional opsonization of S. aureus coated with sIgA1 or sIgA2 with complement resulted in both cases in a statistically significant enhanced specific H2O2 release by PMN (P less than 0.05).

Complement C3↗
PubMed1985

Influence of genetically inherited complement deficiencies on humoral immune response in guinea pigs.

To assess the role of complement in the induction of the humoral immune response, we studied the antibody response of guinea pigs genetically deficient in the second component of the classical complement pathway (C2D-GP) to bacteriophage phi X 174--a T cell-dependent antigen--in comparison with normal guinea pigs and C4D-GP, for which a disturbance in induction of antibody response has been described. We were able to establish a clear dose-response relationship: with low doses of antigen (1 X 10(9) PFU/kg), the antibody response of both complement-deficient strains was grossly impaired as compared with normal guinea pigs. After primary immunization, the peak antibody titer was diminished (1 log10) and declined rapidly; after secondary immunization, the diminution became even more distinct. Both complement-deficient strains had unusual secondary antibody responses almost identical to their primary ones, and amplification of antibody titer, as well as regular isotype switch from IgM to IgG, was absent. By increasing the antigen dose (2 X 10(9) PFU/kg), the antibody responses of the complement-deficient guinea pigs tend to normalize, and when high doses of antigen (1 X 10(10) PFU/kg) were used, the behavior of the complement-deficient animals was nearly indistinguishable from that of normal animals. Partial restoration of the immune response was seen when substituting the genetic complement deficiency by giving serum as source of the missing complement component. The important contribution of the C2 deficiency is given by the now compelling evidence that it is not the missing individual component itself, but rather the common block in sequential activation of C3 via the classical pathway in both complement deficiencies, that is responsible for the impaired humoral immune response, especially at low antigen doses. We therefore postulate that an intact classical pathway contributes to reaching a normal humoral immune response.

Animals↗
PubMed1993

Activation of the complement system by Francisella tularensis lipopolysaccharide.

We have shown by combining lipopolysaccharide (LPS) extracted and purified from Francisella tularensis live vaccine strain (LVS) with normal complement and back titrating with sensitised sheep red blood cells that the LPS activates complement. Deionising the LPS and converting it into the single salt forms of pyridine, ethanolamine and triethylamine altered the ability to activate complement according to the apparent molecular weight due to aggregation. Francisella tularensis LPS activated complement deficient in a component of the alternative pathway (factor B) but failed to activate complement deficient in a component of the classical pathway (C1q). In addition normal complement suspended in ethyleneglycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) which inactivates the classic pathway was not activated by LPS, and we concluded that the LPS activates complement predominantly via the classical pathway. LPS bound to specific monoclonal antibodies activated complement more than LPS alone. An anti-core monoclonal antibody was approximately tenfold more potent when bound to LPS then an anti-O side chain monoclonal antibody in activating complement.

Antibodies, Bacterial↗
PubMed1997

Role of complement in acute tubulointerstitial injury of rats with aminonucleoside nephrosis.

The present work was designed to elucidate the in vivo role of complement in the proteinuria-associated tubulointerstitial injury. Rats were intravenously injected with puromycin aminonucleoside, and massive proteinuria was observed within 5 days. Prominent tubulointerstitial injury characterized by proximal tubular degeneration, tubular dilatation, and leukocyte infiltration were observed 7 days after injection. C3 and C5b-9 were observed in the luminal side of proximal tubular cells. Renal function, assessed by inulin and para-aminohippurate clearance, was significantly decreased. To-assess the role of complement in this model, rats were injected with either cobra venom factor or soluble recombinant human complement receptor type 1 starting at day 3. These manipulations significantly improved tubulointerstitial pathology and para-aminohippurate clearance without affecting the degree of proteinuria. Deposition of C3 and C5b-9 was not detected in the kidney of rats depleted of complement by cobra venom factor. In rats treated with soluble complement receptor, C3 was still detected in the tubules, but deposition of C5b-9 was not observed. Soluble complement receptor was detected at the site of C3 deposition and in the urine. These data strongly suggest that complement plays a pivotal role in proteinuria-associated tubulointerstitial injury and that systemic complement depletion or inhibition of complement in the tubular lumen may diminish the tubulointerstitial damage.

Animals↗
PubMed1995

Decreased levels of complement receptor 1 (CD35) on B lymphocytes in persons with HIV infection.

Previous studies have shown that complement receptor 1 (CR1) expression on erythrocytes is decreased under several conditions including HIV infection and autoimmune diseases. The goal of this study was to determine whether expression of CR1 on peripheral blood B cells, where this receptor plays a role during immune responses, is altered in persons with HIV infection. The B cells from rheumatoid arthritis (RA) patients were also assessed since this represents a group with known complement and B cell abnormalities. The CD19+ B cells from persons with either HIV infection or RA had significantly reduced levels of CR1 when compared with control donors (75 and 72% CR1+ versus 94% CR1+ for control donors). The reduction of B cell CR1 occurred in both the percentage of B cells positive for CR1 and the levels of CR1 found on positive cells. In contrast, CR1 on monocytes was not reduced. As shown in previous studies, CR2 was also found to be reduced on B cells from the HIV-infected persons and there was extensive overlap between the B cell subsets which lacked expression of CR1 and CR2. The complement receptor-negative B cells found in HIV-infected persons were not immature or activated as defined by their lack of expression of CD10 or B7, respectively. Elevated levels of C4d, a classical complement pathway-activation product, were detected in plasma from both HIV-infected and RA patients. These studies suggest that chronic complement activation occurring in persons with HIV infection or RA can affect the complement receptor phenotype of peripheral blood B cells. Since complement receptors are involved in activation of B cells, the subset that lacks CR1 may represent cells that have encountered immune complexes and may therefore be stimulated. Additionally, the downregulation of complement receptors may have significant effects on the ability of B cells to capture and present opsonized antigens.

Antigen-Antibody Complex↗
PubMed1983

In vitro alternative and classical activation of complement by extracts of cotton mill dust: a possible mechanism in the pathogenesis of byssinosis.

Extracts of cotton mill dust (CDE) were shown to activate complement by the classical and alternative pathways. Activation of the classical pathway, presented in this study for the first time, was verified by C1 consumption, C2 destruction, and C4 conversion tests. The component of cotton dust that causes complement activation precipitated in the presence of 20% saturated ammonium sulfate. The data presented suggest that endotoxin is not the principal complement-activating component, as complement activation could not be correlated to endotoxin concentrations of extracts of various parts of the cotton plant. Proteolytic enzymes were also eliminated as possible causative agents of complement cleavage since CDE did not cleave purified C3 in the absence of other complement components. Polyvinylpolypyrrolidone failed to remove the complement-activating component in CDE demonstrating that polyphenolic tannins are not the causative agents. Involvement of complement activation in the pathogenesis of byssinosis could explain in part the mechanism and symptoms of the acute byssinotic reaction.

Byssinosis↗