Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C8”

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 253 records · Page 14Linked to original sources
PubMed1989

Paroxysmal nocturnal hemoglobinuria: the biochemical defects and the clinical syndrome.

Paroxysmal nocturnal hemoglobinuria is a disorder characterized by the lack of membrane proteins affixed to the membrane by an anchor dependent upon phosphatidyl inositol, suggesting that some acquired abnormality in the metabolism of this class of proteins is basic to the disease. Most of the clinical symptoms can be explained by the lack of these proteins. However, much work is needed to understand completely the relationship of the biochemical facts and the clinical syndrome.

5'-Nucleotidase↗
PubMed1991

Human brain prostaglandin D synthase has been evolutionarily differentiated from lipophilic-ligand carrier proteins.

cDNAs for glutathione-independent prostaglandin D synthase were isolated from cDNA libraries of human brain. The longest cDNA insert was 837 base pairs long and contained a coding region of 570 base pairs corresponding to 190 amino acid residues with a calculated Mr of 21,016. Between two cDNA inserts isolated from the two different libraries, nucleotide substitutions were observed at 16 positions, including conservative amino acid substitutions at 2 positions and nonconservative substitutions at 5 positions, indicating genetic heterogeneity of this enzyme in humans. The computer-assisted homology search revealed that the enzyme is a member of the lipocalin superfamily, comprising secretory hydrophobic molecule transporters, showing the greatest homology (28.8-29.4% identity; 51.3-53.1% similarity) to alpha 1-microglobulin among the members of this superfamily. In a phylogenetic tree of the superfamily, this enzyme, alpha 1-microglobulin, and the gamma chain of the complement component C8 form a cluster separate from the other 14 members. The two distinctive characteristics of glutathione-independent prostaglandin D synthase, as compared to the other members of this superfamily, are its enzymatic properties and its association with membranes that were probably acquired after evolutionary divergence of the two lipocalins. Based on the observed sequence homology, the tertiary structure of the enzyme was deduced to consist of an eight-stranded anti-parallel beta-barrel forming a hydrophobic pocket. Furthermore, the Cys-65 residue in the pocket, which is conserved only in the human and rat enzymes but not in other lipocalins, was considered to be a putative active site of the enzyme.

Amino Acid Sequence↗
PubMed1988

The genetic polymorphism of complement component C81 (alpha-gamma) in two Chinese populations.

The genetic polymorphism of the complement component C81 (alpha-gamma) in two Chinese populations (Beijing and Guangzhou) were investigated, using isoelectric focusing followed by an immunoblotting technique. Three common and two rare phenotypes were observed. The homozygote phenotype C81 A1 ascribed to a rare allele C81*A1 was newly detected. The frequencies calculated for the two common alleles were as follows: C81*A = 0.5674, C81*B = 0.4255 for the Beijing population; C81*A = 0.5117, C81*B = 0.4785 for the Guangzhou population. The gene frequencies of the two common alleles of C81 in both Chinese populations were similar to those for the other ethnic groups thus far reported, and there is no statistically significant difference between the Beijing and the Guangzhou populations.

Alleles↗
PubMed1987

First cysteine-rich repeat in ligand-binding domain of low density lipoprotein receptor binds Ca2+ and monoclonal antibodies, but not lipoproteins.

The ligand binding domain of the low density lipoprotein receptor consists of seven cysteine-rich repeats of approximately 40 amino acids each. These repeats, which are located at the NH2 terminus of the protein, are homologous to sequences in complement components C8 and C9. To determine the role of the first repeat (amino acids 2-42), we prepared two plasmids containing expressible low density lipoprotein receptor cDNAs. The first plasmid, p delta R1, lacks only the nucleotides encoding the first repeat. It produced a receptor that bound and internalized lipoproteins and recycled to the cell surface with the same efficiency as the normal receptor. This deleted receptor failed to bind two monoclonal antibodies, IgG-C7 and IgG-15C8, which were shown previously to react with the ligand-binding domain. The second plasmid, pR1, encodes a markedly truncated protein whose extracellular domain consists of the first repeat joined to the transmembrane and cytoplasmic domains. This protein bound the two monoclonal antibodies with the same affinity as the normal receptor, but failed to bind lipoproteins. Binding of IgG-15C8 to the normal receptor and the pR1-encoded protein was Ca2+-dependent, indicating that the first repeat binds Ca2+. We conclude that repeats 2-6 in the ligand-binding domain are sufficient for binding lipoproteins and that the first repeat is highly immunogenic, but is not required for lipoprotein binding.

Antibodies, Monoclonal↗
PubMed1994

Human liver-derived HEP G2 cells produce functional properdin.

Properdin stabilizes the alternative complement pathway C3 convertase and is synthesized by monocytes and myelomonocytic cell lines. Hepatic production of properdin has never been documented, although most other complement components are synthesized by liver. Human liver-derived Hep G2 cells were examined for the ability to produce properdin by using the polymerase chain reaction (PCR). Amplified properdin message was detected by using Southern transfer and hybridization to a murine properdin cDNA probe. Sequencing of the PCR product revealed that the Hep G2 message was nearly identical to the cDNA sequence from U937 cells. Subsequently Hep G2 cultures were stimulated with interleukin (IL-6), 25 micrograms/ml, and culture supernatants were assayed for the presence of properdin by using dot blots. Properdin concentration increased over time, and we found no obvious difference between properdin production by IL-6-stimulated and unstimulated Hep G2 cells. Finally, alternative pathway decay assays confirmed the presence of functionally active properdin in the culture supernatant. Thus, functional properdin is a product of Hep G2 cells, suggesting that biosynthesis of properdin may occur in hepatocytes. Properdin synthesis was not augmented by IL-6, a finding that is consistent with previous observations that properdin is not an acute phase reactant.

Base Sequence↗
PubMed1977

[Inflammation of the uvea--the cellular immune response in the iris (author's transl)].

Ultrastructural analyses of iris biopsies in 17 cases of uveitis with different etiology revealed that all cells involved in immunological reactions are present. Many plasmacells and lymphocytes, but also macrophages and mastcells are found. Destruction of cells and even necrosis as well as damage of blood vessels are run. No specific germs could be demonstrated and etiology was not further elucidated. But there remains no doubt on the immunological nature of uveitis.

Animals↗
PubMed1986

The pore-forming protein (perforin) of cytolytic T lymphocytes is immunologically related to the components of membrane attack complex of complement through cysteine-rich domains.

Structural, functional and immunological similarities between the ninth component of complement (C9) and the lymphocyte pore-forming protein (PFP, perforin) have recently been described (8-10). PFP is shown here to be immunologically related to all other components of the membrane attack complex (MAC) of human complement, namely, C5b-6, C7, C8, and C9. Polyclonal antibodies raised against purified human C5b-6, C7, C8, or C9 react with other components of the MAC and with mouse lymphocyte PFP. The antigenic epitopes shared by human complement proteins and mouse lymphocyte PFP are limited to cysteine-rich domains. Only complement proteins that have been reduced and alkylated elicit the production of crossreactive antibodies when used as immunogens. The nonreduced forms of complement components or lymphocyte PFP neither react with these antibodies nor give rise to crossreactive antibodies. The homologous domains of complement proteins and lymphocyte PFP may play related functions in their attachment to lipid membranes and assembly of membrane lesions.

Animals↗
PubMed1985

Analysis of the specific association of the eighth and ninth components of human complement: identification of a direct role for the alpha subunit of C8.

The basis for the physical association between C8 and C9 in solution was examined by isolating the noncovalently associated alpha-gamma and beta subunits of C8 and determining their respective affinities for C9. Results indicate that only alpha-gamma associates with C9 and this association, though reversible, is complete at near equimolar ratios of each component. Further experiments using purified alpha or gamma revealed that only alpha was capable of forming a stable complex with C9. Although the strength of this interaction was dependent on salt concentration, association was observed in buffer of physiological ionic strength and in human serum. These results establish that the domain on C8 responsible for interaction with C9 is located entirely within alpha. In related experiments, addition of beta to performed dimers of either (alpha-gamma + C9) or (alpha + C9) resulted in complete association of this subunit. These particular results indicate that there are two physically distinct sites on alpha that separately mediate association of alpha with beta and with C9. Furthermore, occupation of one site does not impair interaction at the other.

Complement C8↗
PubMed1982

Transmembrane channel formation by complement: functional analysis of the number of C5b6, C7, C8, and C9 molecules required for a single channel.

Earlier studies have shown that sequential treatment of resealed erythrocyte ghosts with C5b6, C7, C8, and C9 leads to insertion of hydrophobic peptides from these complement proteins into the membrane and assembly of transmembrane channels. The number of molecules of each of the proteins required for assembly of the membrane-associated channel structure was evaluated by measuring the quantitative relationship between the doses of the individual proteins and the release of two trapped markers, sucrose and inulin, from ghosts after channel formation. The incubation period was sufficient to attain equilibrium of marker distribution between the ghosts and the extracellular fluid. Two markers of different size (sucrose and inulin, 0.9 and 3 nm molecular diameter, respectively) were used in order to develop information on the molecular composition of small and large channels, respectively. We found that participation of C5b6, C7, and C8 in channel formation displayed one-hit characteristics, regardless of marker size. By contrast, the participation of C9 was one-hit with respect to the sucrose marker, whereas with respect to the inulin marker the C9 reaction was multi-hit. Our results are compatible with the view that these markers are released through a channel structure in the membrane that is a monomer of C5b--9 of the composition C5b61 C71C81C9n, in which n = 1 for channels permitting passage of sucrose and n = 2 for channels allowing transit of inulin.

Animals↗
PubMed1986

Restriction in the lytic efficiency of complement of different erythrocyte targets: a re-examination of the activities of horse C8 and C9.

Differences in the lytic efficiency of different complement sources have frequently been observed. This effect has been shown to be related to both the species of the target erythrocyte and the species composition of terminal complement components within the 5b-9 membrane attack complex. The majority of studies have indicated that the source of C9 is critical in controlling the range of erythrocyte species that can be lysed efficiently. One exception to this general finding was the report by Lachmann et al., 1973 (Immunology 24, 135-145), using horse serum as a complement source. In that study, horse C8 rather than C9 was implicated as the critical component. In this study, we have re-examined this observation and find that the restricted hemolytic potential of horse complement correlates absolutely with the presence of horse C9. The reason for the differences between our findings and those of the earlier study are discussed.

Animals↗
PubMed1984

Detection of terminal complement components in experimental immune glomerular injury.

Complement mediates glomerulonephritis by inflammatory cell-dependent and non-inflammatory cell-independent effects on glomerular permeability. The latter may involve terminal components of the complement system. We examined several models of immunologic renal injury in the rat by immunofluorescence (IF) for terminal complement components C5, C6, C7, and C8 in glomeruli using antisera to human C5-8, which cross-react with the analogous rat complement components. Rats with the heterologous and autologous phases of passive Heymann nephritis (PHN) had proteinuria and 1 to 2+ capillary wall deposits of heterologous or rat IgG, rat C3, and C5-8. Complement depletion with cobra venom factor (CVF) significantly decreased proteinuria in both models and prevented deposition of all complement components. Rats with active Heymann nephritis had similar deposits of rat IgG and C5-8. Rats with anti-GBM nephritis and aminonucleoside nephrosis had severe proteinuria which was not affected by CVF treatment and deposits of C5-8 were absent. The presence of terminal complement components in immune deposits in experimental glomerular disease correlates with a functional role for complement in mediating glomerular injury. These data support the hypothesis that the terminal complement pathway may be a major mediator of some types of immune glomerular injury.

Animals↗