Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C1q”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1996

Perforant path transection induces complement C9 deposition in hippocampus.

The presence of complement system proteins in amyloid plaques and the up-regulation of several complement mRNAs in neurons and glial cells in affected brain regions during Alzheimer disease (AD) provided a basis for further examination of complement protein expression in a rodent lesion model of AD. Perforant path transection in rats was used as a model for the degeneration of entorhinal cortex (EC) layer II neurons and the consequent deafferentation of the hippocampus that occurs during AD. Immunostaining for C9, a key terminal component of the complement cascade membrane attack complex (MAC), showed extracellular C9 deposition in parenchyma around the EC wound and in hippocampus as early as 1 day, and disappeared by 14 days postlesion. Apoptosis of EC layer II neurons was seen and was presumably due to severing of their axonal projections to the hippocampus by the transection lesion. However, apoptotic EC layer II neurons were not immunostained by anti-rat C9 antibody, suggesting complement was not involved in inducing apoptosis. In the deafferented hippocampus, extracellular C9 immunostaining was localized to the dentate gyrus middle molecular layer, a region of synaptic loss, dendritic degeneration, and early synaptogenesis. In addition, intracellular C9 immunostaining was seen only in select hippocampal interneurons. Dentate gyrus granule neurons and pyramidal neurons were not C9 immunostained. Clusterin (SGP-2), a soluble inhibitor of the MAC that is up-regulated in AD, was also detected in the wound area (extracellular), the dentate gyrus middle molecular layer (extracellular), and intracellularly in scattered hippocampal interneurons. The data support the hypothesis that the complement system generally participates in responses to brain injury, as well as in AD.

Afferent Pathways↗
PubMed2006

Self, non-self, and danger: a complementary view.

Complement is a sophisticated system of molecules that is critical to the functional integrity of the body. Initially considered as a defense system to ward off infections, it becomes increasingly clear that the complement system is one of the most important humoral systems to sense danger, i.e., to recognize conserved patterns on pathogens and on altered/damaged self. In addition to this important role in danger recognition, the complement system has the ability to translate the danger information into an adequate cellular innate or adaptive immune response. This is accomplished by two distinct mechanisms: (a) danger sensors that have recognized altered cells or pathogens can directly activate cell-bound receptors (e.g., C1q/C1q receptor interaction), and/or (b) danger sensors initiate cleavage of complement factors C3 and C5, the fragments of which acquire the ability to bind to complement receptors and/or regulators. It is the specific interaction of the danger sensors and of the cleavage fragments with distinct cell-bound receptors/regulators that directs the immune response toward an innate or an adaptive phenotype. Further, the expression pattern of the complement receptors critically impacts the shape of the immune response. Complement has the ability to discriminate between physiological and pathological danger, i.e., physiological cell death and death in response to injury. In the former case, cells are merely flagged for enhanced phagocytosis (by C3 fragments) without accompanying inflammation (through CR3), whereas in the latter case inflammatory signals are accessorily triggered (e.g., by the release of ATs, which recruit and activate neutrophils, eosinophils, etc.). This function is of major importance for apoptotic cell clearance and tissue repair but plays also important roles in fibrotic tissue remodeling in response to chronic tissue injury. Further, complement cleavage fragments may prevent the development of maldaptive immune responses at the mucosal surface. Here, complement fragment C5a does not act as a danger transmitter but as a "homeostasis transmitter," as its interaction with the C5a receptor on DCs provides a signal that prevents DCs from activating CD4+ T cells. The generation of regulatory T cells in response to CD46 ligation may have a similar function, as injured cells lose CD46 expresssion, which may lead to decreased proliferation of Tregs and, consecutively, increased production of T effector cells. Although we are still at the beginning of understanding the complex interaction patterns within the complement system, recent data suggest substantial crosstalk between the signaling pathways downstream of complement receptors and other receptors of the innate immune system that function as immune sensors and/or transmitters (i.e., TLRs, FcgammaRs130,131). Given the importance of complement as a sensor and effector system of innate and adaptive immune responses, a complement-related view of the immune system might help to unravel some enigmas of autoimmunity, allergy, and transplantation.

Anaphylatoxins↗
PubMed1983

DNA antibodies and complement in SLE patients. A follow-up study.

Sixty-seven patients with systemic lupus erythematosus (SLE) were followed up for 3-19 months (mean 12) in a prospective study. The activity of SLE was estimated on clinical grounds and correlated with DNA antibody and complement levels. The disease reactivations consisted mostly of articular and cutaneous symptoms. There were 17 relapses and 22 complicating infections during the follow-up period. The levels of antibodies to native, double-stranded (ds) DNA (P less than 0.001) and antibodies to denatured, single-stranded (ss) DNA of IgG class (P less than 0.001) and C3 (P less than 0.001) correlated best with disease activity, which was estimated on the clinical symptoms and signs. These assays were not reliable, however, in predicting minor exacerbations. The levels of IgM class ss-DNA antibodies were significantly higher in SLE patients without nephritis than in SLE nephritis patients. In most cases, the combination of IgG class ss-DNA antibody and complement (C3 and CH50) determinations differentiated SLE relapse from infection.

Autoantibodies↗
PubMed1981

The absence of circulating immune complexes in patients with ankylosing spondylitis.

Sera from 50 patients with well-defined ankylosing spondylitis were examined for circulating immune complexes using both a Clq binding (fluid phase) assay and a Raji cell assay. No more than five of the patients assessed had circulating immune complexes by either one of these techniques and none were positive in both. This result is in contrast to the high prevalence in sera from unselected patients with rheumatoid arthritis and systemic lupus used as positive controls.

Adult↗
PubMed1986

Separation and characterization of complement-fixing immune complexes in juvenile rheumatoid arthritis patients.

Immune complexes (IC) in sera from patients with juvenile rheumatoid arthritis (JRA) were isolated by the use of immunoabsorbent columns. Sera from 14 JRA patients (four seropositive for 19S IgM RF and 10 seronegative, but nine having hidden 19S IgM RF) were analyzed by the anti-human Clq (alpha HClq) and anti-human C3 (alpha HC3) columns. The columns were sequentially eluted with veronal buffer, 0.02 M EDTA, 0.5 M NaCl, and 1 M propionic acid. By the alpha HClq column, IgM RF were detected in at least one of the separated IC fractions of 13 of 14 patients and IgG RF in three patients. By the alpha HC3 column, only five patients demonstrated IgM RF and only one IgG RF in the eluted fractions. On sucrose density gradient analysis (SDGA), all IC were demonstrated in the peaks greater than or equal to 19S.19S IgM RF were demonstrated by ELISA in all 14 patients, but IgG RF in only three. These studies demonstrate that complement-fixing 19S IgM RF, IgG, and IgG RF containing IC can be detected in the serum of JRA patients.

Antibodies↗
PubMed1986

Dietary bovine antigens and immune complex formation after intravenous immunoglobulin in common varied immunodeficiency.

Previously we have shown that the sera of hypogammaglobulinemic patients may contain large amounts of antigenically intact foreign protein of dietary origin, presumably due to the absence of an adequate gastrointestinal secretory immune barrier. In these studies we show that the intravenous infusion of immunoglobulin in these patients may result in high levels of immune complexes postinfusion and that at least one constituent of these complexes is likely to be bovine casein.

Agammaglobulinemia↗
PubMed1984

Deficiency in C3b receptors on neutrophils of patients with chronic granulomatous disease and hyperimmunoglobulin-E recurrent infection (Job's) syndrome.

C3b receptor (CR1) expression by neutrophils (PMNs) and erythrocytes (Es) from patients with chronic granulomatous disease (CGD) or with hyper-IgE, frequent infection (Job's) syndrome was compared with that of control subjects. The control subjects consisted of one group of patients with infections and a second group of normal, healthy individuals. Three quantitative assays were used: rosette formation with C3b-coated cellular intermediates (EAC43b), binding of radiolabeled monoclonal anti-CR1 ([125I]anti-CR1) to PMN surfaces, and binding of the antibody to nonidet P-40 (NP-40) extracts of PMNs and Es in an immunoradiometric assay. Rosette formation by the PMNs of five male CGD patients was about 50% of that of paired normal control subjects, whereas the rosette formation of three female CGD patients was similar to that of the control subjects. Surface binding of [125I]anti-CR1 to PMNs of 10 CGD patients was about half that of the normal subjects (mean percent binding was 2.33% for the CGD patients vs. 3.86% for the normal subjects, giving a difference of -1.53 +/- 0.22%, P less than 0.001 by the paired-sample t test). The degree of PMN binding was similarly low for both the male and the female CGD patients. Conversely, the binding of anti-CR1 to the PMNs of 11 infected control patients appeared to be similar to that of the normal subjects (4.51% for the patient vs. 4.21% for the paired normal subjects). The infected control group originally included four Job's syndrome patients, and when this subgroup was analyzed separately, their PMNs were shown to bind significantly less anti-CR1 than did the PMNs of the normal subjects (P less than 0.01 by the paired-sample t test). In contrast, the other infected control patients showed higher-than-normal levels of anti-CR1 binding (P less than 0.05). When compared to that of the normal subjects, the total CR1 quantitated in PMN extracts was also lower than normal in CGD patients (P less than 0.01 and in the PMN extracts of eight Job's syndrome patients tested (P less than 0.01). The PMNs of the other infected control subjects were not significantly different from those of the normal subjects in total CR1 expression. Extracts of Es from Job's syndrome patients also had fewer than normal CR1 (P less than 0.02). On the other hand, CR1 levels in E extracts from the CGD patients and the other control patients were similar to those in the normal control subjects. Quantitations of C3, C4, and factor B were normal in CGD.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Antibody Complex↗
PubMedDate not supplied

The role of circulating immune complexes in the pathogenesis of diabetes mellitus.

We have studied soluble immune complexes (IC) in the sera of both insulin-dependent and non-insulin-dependent diabetics by a variety of non-specific techniques and also by a method that detects specifically insulin-anti-insulin IC. Our screening studies, detailed in the first section of this work, showed that insulin-anti-insulin IC appear not to be the only type of IC present in diabetics. Non-specific screening tests gave practically identical percentages of positive results in insulin-dependent and non-insulin-dependent diabetics. However, the agreement between different screening tests was poor. We propose the use of 'IC scores' (numerical expressions of the general trend of several screening tests performed with one given serum sample) for the statistical analysis of correlations between the presence of soluble IC and clinical evidence of diabetic microangiopathy. As expected, the use of 'scores' minimized false positive or negatives and considerably enhanced statistical correlations between levels of IC and proteinuria, nephropathy, retinopathy, peripheral neuropathy, and peripheral vasculopathy. The second section of this report describes our isolation studies, which provided definitive proof for the existence of soluble insulin-anti-insulin IC and allowed us to carry out the first successful studies of the biological properties of soluble IC purified from the sera of diabetic patients, as detailed in the third section of this report. Such IC-induced platelet aggregation and activation which in vivo could lead to the development of microvascular lesions could explain, at least in part, the abnormalities in platelet function seen in diabetics. Although the precise mechanisms by which soluble IC could induce pathological damage in diabetics have not been totally clarified, we have obtained sufficient evidence to prove that antigen-antibody complexes exist in diabetics, are associated with higher frequencies of complications, and have the capacity to interact with cells in a potentially pathogenic fashion.

Antigen-Antibody Complex↗
PubMed1988

Role of platelet factors and serum complement in growth of fibroblasts with high-affinity Clq complement receptors.

Cultures of human diploid fibroblasts are heterogeneous in that a subpopulation interacts via high-affinity receptors with the globular head regions of the Clq complement protein. Growth and synthetic properties of these cells are characteristic of cells residing in healing wounds and inflammatory lesions. At these sites, fibroblasts are exposed to regulatory molecules such as complement components and factors released from blood platelets. We assessed the effects of native complement proteins and platelet-derived factors on proportions and phenotypic stability of high-affinity and low-affinity receptor cells generated from explants of adult and embryonic connective tissue, using radioligand binding assays and immunofluorescence analysis by flow cytometry. Fibroblasts expressing high-affinity Clq receptors could be generated from explants only when factors from platelets were present in the medium; native complement proteins were not essential. High-affinity receptor cells could be generated only from tissue; they could not be generated by incubating cultures of the low-affinity receptor phenotype in medium containing platelet-derived factors. High-affinity receptor cells, once established from explants in the presence of platelet-derived factors, persisted through many replications in the absence of platelets. We obtained the same fibroblast phenotypes from embryonic skin as from adult gingiva, but the proportion of high-affinity receptor cells from skin was much greater. We conclude that factors derived from platelets are essential for generating cultures containing fibroblasts expressing high-affinity Clq receptors, but not for their maintenance. High-affinity receptor cells may comprise a rapidly dividing subpopulation giving rise only to like progeny or to other, more differentiated cells.

Adult↗
PubMed2005

Fatal CNS vasculopathy in a patient with refractory celiac disease and lymph node cavitation.

Celiac disease is an enteropathy occurring in genetically predisposed individuals due to a dietary intolerance to gluten. Patients with celiac disease may develop a neurological disorder of unknown cause, although autoimmune mechanisms are suspected. We report on a 56-year-old man with celiac disease, who became refractory to a gluten-free diet and died of a rapidly progressive encephalopathy. Magnetic resonance imaging indicated focal lesions of the cerebellum and brainstem, and electrodiagnostic studies suggested an axonal neuropathy. Autopsy revealed a flattened small-bowel mucosa with intraepithelial lymphocytosis, a spectrum of degenerative changes of the intra-abdominal and mediastinal lymph nodes, including cavitary degeneration, and splenomegaly. Histologically, the lymph nodes showed pseudocyst formation and lymphocytic vasculitis with fibrinoid necrosis, and sections of the brain exhibited fibrinoid degeneration of small blood vessels, sparse perivascular lymphocytic infiltrates, and perivascular ischemic lesions. Identical T-cell clones were identified in the duodenum, stomach, lymph nodes, and spleen. This patient had an unusual neurological disorder related to a vasculopathy, probably mediated by a circulating neoplastic clone of activated T cells.

Brain Diseases↗
PubMed1997

Nephrotic syndrome and Hodgkin disease in children: a report of five cases.

UNLABELLED: This report documents the occurrence of a nephrotic syndrome in five children with Hodgkin disease. In two cases the nephrotic syndrome predated the diagnosis of lymphoma by 6 months and 12 months respectively, while in the other three, the two disorders occurred simultaneously. The nephrotic syndrome resolved in four cases during effective treatment for active Hodgkin disease, while proteinuria remained unchanged in the fifth case with partial control of the lymphoma. The occurrence of a nephrotic syndrome as a manifestation of active Hodgkin disease suggests that some immunological abnormalities play a role in the pathogenesis of the association. CONCLUSION: The possibility of glomerular dysfunction although rare must be considered and actively looked for in all cases of Hodgkin disease. Similarly, any unusual sign or symptom noted in patients with nephrotic syndrome, particularly receiving or having received immunosuppressants, requires thorough investigation to determine the presence or absence of lymphoma.

Adolescent↗
PubMed1987

IgG binding to cytoskeletal intermediate filaments activates the complement cascade.

The cellular plasma membrane becomes permeable to macromolecules during the cell injury process. This results in exposure of the interior of the cell to plasma proteins and to high-affinity binding of the Fc part of IgG to intermediate filaments (Hansson, G K, Starkebaum, G A, Benditt, E P & Schwartz, S M, Proc natl acad sci USA 81 (1984) 3103). Such IgG binding could be an early step in a process that serves to eliminate the injured cell. We have now identified its effect on the complement system. Intermediate filaments were reconstituted in vitro from purified vimentin, and incubated with plasma proteins. Cross-linker experiments showed binding of the heavy chain of IgG to vimentin, indicating that the vimentin protein carries an Fc-binding site. In contrast, no direct binding of complement factor Clq to vimentin could be detected. Binding of both IgG and Clq could, however, be detected by immunofluorescence when cytoskeletons of cultured endothelial cells were incubated with fresh serum. Therefore, IgG binding to filaments in the presence of serum is accompanied by Clq binding to IgG. This was in turn followed by fixation of C4 and C3 to intermediate filaments in a process that was dependent on both Ca2+, Mg2+ and Clq, indicating that it was part of a complement activation via the classical pathway. Exposure of fresh serum to intermediate filaments also resulted in production of the anaphylatoxic complement cleavage fragment. C3a, with a dose-response relationship between the amount of filaments present and the amount of C3a generated. Chemotactic activity towards granulocytes and monocytes was also generated by exposure of serum to intermediate filaments, and this activity was dependent on the presence of complement factor C5 and on the classical complement activation cascade, implying that it was due to the C5a peptide. Exposure of the interior of the cell to plasma proteins thus results in binding of IgG to intermediate filaments and activation of the complement cascade via the classical pathway. This, in turn generates bioactive mediators which may recruit leukocytes to the injured cell (C5a) and have profound effects on vascular permeability (C3a, C5a). We propose that this is part of a scavenger mechanism for the elimination of damaged cells.

Binding Sites↗