Biomedical subjects

S Meri

Publications and source records attributed to S Meri.

131 records · Page 8Linked to original sources

PubMed1985

Complement activation by circulating serum factors in human glomerulonephritis.

Factors with the ability to induce a minimum of 20% C3 conversion in normal human serum (NHS) were demonstrated in the sera of nine glomerulonephritis (GN) patients. The nature of these factors was heterogeneous allowing their division into at least three different groups. First, in three cases (membranoproliferative or acute GN) they exhibited the characteristics of C3 nephritic factor, an IgG autoantibody stabilizing the alternative pathway (AP) C3 convertase, C3bBb. Secondly, the serum of one patient (SLE like syndrome, mixed cryoglobulinaemia) with an activator of both pathways and profound hypocomplementaemia showed a temperature-dependent precipitation against autologous and homologous polyclonal IgG. Immunochemical analysis suggested this activity to be due to a monoclonal IgM kappa rheumatoid factor. By gel filtration the C3 converting activity was found in the high molecular weight fractions containing the cryoprecipitable IgM-IgG complexes. Finally, in five cases the exact nature of C-activating factors remained unknown. In four of these the factors were heat labile (30 min at 54 degrees C) C activators in association with post-streptococcal glomerulonephritis. The results suggest that the various C activating factors, possibly distinct from 'classical' immune complexes, are indicators of different types of pathogenetic mechanisms in certain forms of GN.

Adult↗

PubMed1984

Complement in chronic secretory otitis media. C3 breakdown and C3 splitting activity.

Occurrence of in vivo C3 breakdown and in vitro C3 splitting activity was studied in serum and middle-ear effusion (MEE) samples from 30 children with chronic secretory otitis media (SOM). The MEE showed strongly elevated levels of both low- and high-molecular-weight C3 breakdown products, along with decreased factor B, C4, and C3 levels. Total hemolytic complement component activity was virtually absent from MEE. The MEE fluids were found to contain C3 splitting factors as demonstrated by their high capacity to convert C3 in vitro from fresh normal human serum. This activity was not inhibited by the classic complement pathway inhibitor, 0.01M ethylene glycol tetra-acetic acid with 0.005M magnesium chloride. The results suggest that a strong local complement activation has taken place and that the factors responsible are present in the MEE of patients with SOM.

Antigen-Antibody Complex↗

PubMed1981

An immunofluorescence assay for complement activation by the classical pathway.

The functional integrity of classical complement pathway components was determined by an immunofluorescence (IFL) assay based on the capacity of cytoskeletal intermediate filaments (IMF) to bind C1q and to activate the complement pathway. The assay uses IMF-rich capillary endothelium of human term placentae as complement-activating substrate. IFL staining for bound C1q, C4 and C3 was demonstrated after incubation of the tissue sections with normal human sera in dilutions up to 1 : 80. Known inhibitors of C1q binding and inhibitors fo C3 convertase formation prevented binding of complement components. Eight of 100 sera from patients showed negative or reduced binding of complement whereas all of 100 control sera from healthy individuals were positive in the assay. Four negative patients' sera were studied further: 3 had markedly reduced hemolytic activity and normal levels of C3 and C4. The IFL assay for complement activation provides a simple method of evaluating complement deficiencies and of studying mechanisms and inhibitors of complement activation.

Autoantibodies↗

PubMedDate not supplied

Factor H and disease: a complement regulator affects vital body functions.

Factor H is a multidomain and multifunctional protein. As a complement regulator factor H determines the fate of newly formed C3b and controls formation and stability of C3 convertases both in the fluid phase and on cell surfaces. In addition, this plasma protein displays functions outside complement control as it has been suggested to act as an adhesion protein, to be a ligand for the cellular integrin receptor CR3 (CD11b/CD18) and to display chemotactic activity. Genetic and pathophysiological analyses describe a role for factor H in vital body functions. Depletion or the absence of factor H due to genetic reasons leads to unrestricted C3 consumption. A reduced amount of factor H in plasma or mutations within the factor H gene may lead to glomerulonephritis (type II MPGN) or hemolytic uremic syndrome (HUS). Certain pathogenic organisms have been shown to evade complement attack by binding factor H from the host. Such specific factor H binding components have been demonstrated on the surface of microbes, e.g., Streptococcus pyogenes and Neisseria gonorrhoeae. Here, we summarize the current knowledge how abnormalities in function of the central complement regulator factor H are associated with human diseases.

Animals↗

PubMedDate not supplied

FHL-1/reconectin and factor H: two human complement regulators which are encoded by the same gene are differently expressed and regulated.

FHL-1/reconectin and factor H are two human complement regulators which are encoded by a single gene. FHL-1/reconectin contains the first 7 of 20 SCR protein domains of factor H and has four unique residues attached to its C-terminal end. The overlapping region of 445 amino acids explains the related complement regulatory functions of the two proteins. However, unique biological functions have also been reported for FHL-1/reconectin, such as cell adhesion and binding to microbial surfaces. Both proteins are synthesised and secreted by the liver. Extrahepatic synthesis occurs in a wide variety of cells, e.g. in monocytes, fibroblasts or neuronal cells. Unexpectedly, FHL-1/reconectin and factor H exhibit distinct expression patterns. This is also observed in disease situations such as in rheumatoid arthritis or malignancies. In rheumatoid arthritis a potentially protective role is suggested by the local synthesis of both FHL-1/reconectin and factor H in synovial fibroblasts and their induction by the anti-inflammatory agent dexamethasone and the cytokine IFN-gamma, but not by TNF-alpha. FHL-1/reconectin is overexpressed in certain tumor cells such as glioblastoma, conferring an exceptional resistance to such cells against complement mediated lysis. Although FHL-1/reconectin and factor H are encoded by a single gene, regulated by the same gene promoter and initiate transcription at the same start site, their transcripts are differently regulated. The putative control levels, which are responsible for this complex regulation, include transcript elongation, RNA processing, alternative splicing and differential poly(A) site selection.

Arthritis, Rheumatoid↗