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At least 487 records · Page 27Linked to original sources
PubMed1982

Receptors for complement on echinoid phagocytes. II. Purified human complement mediates echinoid phagocytosis.

The ingestion of sheep erythrocytes (E) coated with specific IgM antibody (EA) and various purified human complement components (EAC 1, EAC 14, EAC 142, EAC 1423b, EAC 43b) by echinoid phagocytes was examined. E, EA, EAC 1, EAC 14 and EAC 142 were ingested at a similar and very low level, while a strong opsonic effect was found by coating red cells with purified C 3 (EAC 1423b and EAC 43b). When erythrocyte-bound C 3b was converted to the hemolytically inactive C 3bi, the opsonic effect was markedly increased. Conversion of C 3bi to C 3d resulted in a total loss of opsonic activity. A similar response pattern was found when binding of erythrocytes to mouse macrophages was recorded. Since it cannot be ruled out that phagocytes convert C 3b to C 3bi by endogeneous C 3 inactivator, it is concluded that echinoid phagocytes display CR3 (C 3bi) and possibly also CR1 (C 3b) receptors, while CR2 (C 3d) receptors are lacking.

Animals↗
PubMed1981

A kinetic analysis of immune-mediated clearance of erythrocytes.

A mathematical expression has been derived that successfully correlates the kinetic data for the immune-mediated clearance of red blood cells. The expression resulted from the solution of differential equations arising from a clearance mechanism that was, essentially, consistent with that described by Schreiber and Frank. The mathematical expression correlated data for both IgG-and IgM-mediated reactions. Four different rate constants appear in the final kinetic equation; these constants, which measure the rates of the various steps in the clearance process, were evaluated by an iterative curve-matching process. The values of the rate constants were found to be dependent upon type of sensitizing immunoglobulin, number of C1-fixing sites, and several known immune system modifiers. Correlation of the derived rate expression with the experimental data provided a critical test for the Schreiber-Frank mechanism and the values of the rate constants provided additional insights into the immune clearance process.

Animals↗
PubMed1980

Decreased Fc and complement receptors on the phagocytes of asthmatic children.

Surface receptors of polymorphonuclear (PMN) and mononuclear phagocytes for Fc portions of immunoglobulins and complement were studied in 57 asthmatic children and 23 normal controls. Erythrocyte-antibody complexes (EA) were used to detect the Fc receptors and erythrocyte-antibody-complement complexes (EAC) to detect complement receptors. Both the mean percentages of PMN and monocyte with Fc and complement receptors of asthmatic children were significantly lower than those of normals. Moreover, in allergic patients both the numbers of PMN with Fc and complement receptors decreased significantly after incubation with allergen.

Adolescent↗
PubMed1995

Terminal complement pathway activation and low lysis inhibitors in rheumatoid arthritis synovial fluid.

OBJECTIVE: To investigate terminal complement activation and lysis inhibitors in rheumatoid arthritis (RA). METHODS: C5a, vitronectin and clusterin were quantitated by enzyme immunoassays in plasma and synovial fluid (SF) in RA (n = 30) and osteoarthritis (OA) (n = 11). RESULTS: In RA the concentration of C5a was 3-fold increased in plasma (21.9 vs 7.2 micrograms/l) and 5-fold increased in SF (7.8 vs 1.7 micrograms/l) compared to OA. The SF/plasma ratios for C5a, vitronectin and clusterin were 0.35, 0.36 and 0.23, respectively, not significantly different in the 2 diseases. CONCLUSION: SF terminal pathway activation in RA combined with low local levels of lysis inhibitors might allow lytic or sublytic attacks on local cells, resulting in inflammation and cell damage.

Arthritis, Rheumatoid↗
PubMed1995

Characterization of a complement receptor 2 (CR2, CD21) ligand binding site for C3. An initial model of ligand interaction with two linked short consensus repeat modules.

Human CR2 (CD21, EBV receptor) is an approximately 145-kDa receptor and a member of the regulators of complement activation gene family. Regulators of complement activation proteins are characterized by the presence of repeating motifs of 60 to 70 amino acids that are designated short consensus repeats (SCR). CR2 serves as a receptor for four distinct ligands. Three of these ligands (complement C3, gp350/220 of EBV, and CD23) interact with the amino terminal 2 of 16 SCR (SCR 1 and 2). Previous studies have determined that at least four sites are important in allowing CR2 to efficiently bind EBV. Two of these sites are also important for binding mAb OKB7, a reagent that blocks both EBV and iC3b/C3dg binding to CR2. We have identified and characterized important sites of iC3b ligand binding by utilizing human-mouse CR2 chimeras, a rat anti-mouse CR2 mAb designated 4E3 that blocks receptor binding to C3, and human CR2-derived peptides. In addition to demonstrating an important role for the same sequence in SCR 1 that is part of the mAb OKB7 and EBV binding site, we have identified a new region within SCR 2 that interacts with C3. These results, when compared with a model of a dual SCR solution structure derived from human factor H SCR, predict that two distinct largely surface-exposed sites on CR2 interact with iC3b. A relative twist of 130 degrees about the long axis of the second SCR in this model would be necessary for these sites to form a single patch for iC3b binding on CR2.

Amino Acid Sequence↗
PubMed1994

Peripheral nerve injury induces Schwann cells to express two macrophage phenotypes: phagocytosis and the galactose-specific lectin MAC-2.

In N mice, peripheral nerve injury is followed by the normal rapid progression of Wallerian degeneration: Schwann cells proliferate and lose their myelin, which is phagocytized and metabolized by blood-borne macrophages. The role of Schwann cells in myelin phagocytosis is debated. Additionally, the molecular mechanisms underlying myelin phagocytosis by the two cell types are not well understood. To elucidate the role of Schwann cells as phagocytes we studied, electron microscopically, in vivo and in vitro degenerating, frozen, and neuroma nerve segments. The major cell types composing these tissues differed: Schwann and macrophages in in vivo degenerating; Schwann in in vitro degenerating; macrophages in frozen; Schwann, macrophages, and fibroblasts in neuroma nerve segments. Both macrophages and Schwann cells phagocytized myelin. We further studied, by immunocytochemistry and immunoblot analysis, the expression of molecules that are characteristically displayed by inflammatory and mature murine macrophages: MAC-1 (the C3b complement receptor), MAC-2 (a galactose-specific lectin), the Fc receptor, and the F4/80 antigen. All were detected in the macrophage-rich, in vivo degenerating, frozen, and neuroma nerve segments. Surprisingly, MAC-2 was also expressed in the macrophage-scarce, Schwann-rich, in vitro degenerating nerve. Immunocytochemistry and immunoblot analysis of isolated non-neuronal cells revealed that both macrophages and Schwann cells displayed MAC-2 on their surface and in their cytoplasm. Morphometry unveiled that galactose and lactose specifically inhibited myelin phagocytosis, as predicted if MAC-2 was mediating myelin phagocytosis by lectinophagocytosis (lectin-mediated phagocytosis). The role of MAC-2 in mediating myelin phagocytosis was further supported by two observations made in W mice that display very slow progression of Wallerian degeneration. First, the failure to degenerate in vivo was associated with deficient MAC-2 production. Second, degeneration that occurred in vitro was associated with MAC-2 production. Furthermore, a strong positive correlation between levels of MAC-2 expression and the extent of myelin destruction by phagocytosis was observed over a wide range of values.

Animals↗
PubMed1993

The temporal relationship between urinary C5b-9 and C3dg and clinical parameters in human membranous nephropathy.

We have previously reported that urinary excretion of the complement activation products C3dg and C5b-9 in human membranous nephropathy (MN) correlated with clinical outcome in a cross-sectional analysis. We report here the results of a retrospective longitudinal study of the temporal relationship between urinary C3dg and C5b-9 excretion and clinical parameters. A group of 23 adult patients with biopsy-proven MN were studied over a mean time period per patient of 3.5 years. Freshly voided urine samples were collected regularly; C3dg and C5b-9 were measured by ELISA (mean number of samples per patient = 13). During the period of the study, nine patients with declining renal function (group A) were treated with a standard steroid regimen. Serum creatinine had improved or stabilized in seven of these patients at the end of treatment. All nine patients were excreting C3dg and C5b-9 before treatment. Six other patients with declining renal function (group B) were not treated with steroids because of clinical contraindications. Serum creatinine continued to increase during the study in four of these six patients. C3dg and C5b-9 were present in the urine samples of these six patients on the majority of dates tested. Eight patients maintained stable renal function during the study (group C), either normal (6 patients) or impaired (2 patients). Of these patients, six were consistently negative for urinary C3dg and C5b-9 despite persistent proteinuria, and one patient who was initially positive became negative within 15 months, and remained negative for the rest of the study period. One patient was positive on one of 12 occasions tested. These results suggest that urinary complement activation products indicate ongoing active glomerular damage and may prove to be important determinants for the introduction and monitoring of therapy.

Complement Activation↗
PubMed1996

Ultrafiltration after cardiopulmonary bypass in children: effects on hemodynamics, cytokines and complement.

OBJECTIVES: The purpose of the study was to evaluate the clinical and hemodynamic effect of intraoperative extracorporeal ultrafiltration (UF) and its potential in reducing the plasma concentration of circulating cytokines and complement activation products following open heart surgery in children. METHODS: Eighteen children with congenital heart disease were prospectively randomized into a control group (n = 9) and a group who underwent UF (n = 9). Serial plasma samples for measurements of circulating cytokines (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF), and its soluble receptor (sTNF receptor)), and complement factors (C3 activation products (C3a and C3bc) and terminal complement complex (TCC)) were obtained before, during and up to 48 h after cardiopulmonary bypass (CPB). A pulmonary artery thermodilution catheter was introduced preoperatively for hemodynamic monitoring. RESULTS: Postoperative hemodynamics were similar in both groups. Plasma levels of IL-6, sTNF receptors, C3a, C3bc and TCC increased significantly perioperatively (P < 0.01) in both groups. TNF was detected transiently in 16 patients perioperatively and in 4 of the 9 ultrafiltrate samples in concentrations similar to the plasma levels. Complement activating products were not detected in the ultrafiltration samples except for small amounts of C3a in two cases. Compared to the control group the plasma levels of C3a, C3bc and TCC were unaffected by the ultrafiltration procedure. The level of IL-6 and sTNF receptors increased significantly after 15 min of UF but there was no significant difference between the two groups postoperatively. CONCLUSIONS: In this study no clinical or hemodynamic effect was registered after UF. TNF and C3a were occasionally detected in the ultrafiltrate but we were unable to demonstrate reduction of these or any of the other markers tested in the group subjected to ultrafiltration.

Cardiopulmonary Bypass↗
PubMed1995

Mechanism of antigenic variation in Shigella flexneri bacilli. III. Complement sensitivity of S. flexneri 1b strains and their 3b variants selected either as Lac+ recombinants or phage F2 resistant mutants.

Several S. flexneri 1b serotype strains of clinical isolation were compared with their 3b serotype variants isolated either as Lac+ recombinants from crosses of S. flexneri x E. coli Hfr C, or F2-resistant mutants. The studied variants 3b were deprived of type I antigen but acquired type III antigen. They appeared to be less sensitive to killing action of complement present in normal bovine serum although kinetics of killing and its effectiveness differed between the strains.

Animals↗
PubMed1996

Tissue homeostatic role of naturally occurring anti-band 3 antibodies.

Self antigens exposed to the immune system constitutively or in the process of tissue homeostasis may stimulate a TH2 type immunity giving rise to low titer, low affinity naturally occurring antibodies which are involved in actively maintaining peripheral tolerance to self and in tissue homeostatic clearance processes. In reviewing the tissue homeostatic aspect of naturally occurring antibodies to band 3 protein of the human erythrocyte membrane, we address crucial issues of how these and other types of naturally occurring antibodies (NAb) (eg. anti-spectrin NAb) gain functionality and how this can induce opsonization by complement C3b under physiological conditions. Exoplasmic, chemical cross-linking of band 3 protein is sufficient to increase specific anti-band 3 binding under physiological conditions. Formation of oligomers following this non-oxidative cross-linking protocol disfavors a recognition mechanism involving exposure of a neoantigen. New data on NAb binding to erythrocytes further demonstrates that specific binding of any low affinity NAb can only be determined in the presence of whole human IgG and physiological ionic strength, where competition of the predominantly positively charged NAb for binding to the negatively charged cell surface is high. Hence, specific and physiologically relevant binding of low affinity NAb is gained by bivalent binding and suppression of exclusive charge-charge interactions by other NAb sharing the range of pl values. Therefore, many investigations on NAb/cell interactions which have been carried out in the absence of whole IgG have yielded controversial data.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1997

Paraneoplastic syndrome simulating encephalitis in the course of testicular seminoma.

A case of paraneoplastic syndrome diagnosed post mortem in a 68-year-old man with a single submandibular lymphatic metastasis of testicular seminoma is presented. The syndrome developed 3 years after orchidectomy and clinically combined the features of limbic and bulbar encephalitis together with signs of cerebellar degeneration. Histological examination revealed marked loss of cerebellar Purkinje and granular cells and to a lesser extent of cerebral cortical neurons. Additionally axonal injury (spheroids) and multifocal demyelination with sparse lymphocytic infiltrations was observed. Immunohistochemically, strong reaction with monoclonal anti-human IgG in some neurons of cerebellum was detected whereas the reaction with anti-complement (C3b) receptor in corresponding sections was negative. It is suggested that the presented case may represent a "burn out" stage of paraneoplastic syndrome associated with anti-neuronal antibodies, however the isolation of specific antibodies was not performed.

Aged↗