PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Complement System Proteins”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources
PubMed1994

Structure of human factor D. A complement system protein at 2.0 A resolution.

Factor D, an essential enzyme for the activation of the alternative pathway of the complement system, belongs to the serine protease superfamily. The crystal structure of the enzyme was solved by a combination of multiple isomorphous replacement and molecular replacement methods. The present model was refined to an R-factor of 18.8% using 23,681 observed reflections between 7.5 and 2.0 A resolution, with a root-mean-square deviation from standard bond lengths of 0.016 A. The two non-crystallographically related molecules in the triclinic unit cell have distinctive active site conformations. The protein has the general structural fold of a serine protease, but there are several unique amino acid substitutions resulting in significant alterations in the critical loops responsible for catalysis and substrate specificity in serine proteases. Factor D is the first complement serine protease whose three-dimensional structure has been determined.

Amino Acid Sequence↗
PubMed1989

Complement system protein C4 and susceptibility to hydralazine-induced systemic lupus erythematosus.

21 patients with systemic lupus erythematosus induced by long-term treatment with hydralazine were investigated to see whether susceptibility to this syndrome was associated with deficiency of the classical pathway complement protein, C4. 16 of 21 (76%) patients had one or more C4 null (ie, non-productive) alleles compared with 35 of 82 normal subjects (43%). This difference was significant. The HLA-DR4 antigen, known to be in linkage disequilibrium with the C4B null allele, was also significantly more frequent in the patients (14 of 21 patients compared with 31 of 81 normal subjects). Susceptibility to hydralazine-induced lupus, as in idiopathic systemic lupus erythematosus, may depend partly upon genetically determined C4 levels.

Alleles↗
PubMedDate not supplied

[Complement system proteins in the acute phase of myocardial infarction].

Content of C3 and C4 fractions was decreased in blood of patients with acute primary myocardial infarction within the first day of the disease as compared with the level of these fractions observed just after the hospitalization of the patients. These data suggest the activation of the complement system during this first period of the disease. The activation occurred mainly in the usual way as evidenced by single-directed alterations in content of C3 and C4 fractions. The activation of the complement system within the first day of the disease in apparently one of its pathogenetical manifestations. The experimental data are confirmed on participation of the complement system in development of early postischemic impairements of homeostasis.

Acute Disease↗
PubMed1991

Regulation of plaque size and host range by a vaccinia virus gene related to complement system proteins.

A vaccinia virus variant, LC16m8, and its parental Lister (Elstree) strain (LO) were employed to identify the viral gene(s) responsible for plaque size and host range: the large-plaque-forming LO strain but not the small-plaque-forming LC16m8 strain can actively proliferate in Vero (YTV) cells. Previously, we suggested that some particular gene(s) present in the HindIII D fragment of LO DNA was responsible for these biological activities. In the present experiment, the mapping of the putative gene was done by introducing various subfragments of the HindIII D fragment of LO DNA into the gene of LC16m8 strain and screening of the resultant virus variants for the capability of forming large plaques or of proliferating well in Vero cells. The results indicated that an open reading frame (called ps/hr gene) in LO HindIII D fragment was responsible for either plaque size or host range. This gene encoded a polypeptide of 317 amino acids related to the regulators of complement activation (RCA) gene family of mammals. Thus, the present genetic analysis provided direct evidence for a previously unrecognized function of RCA-related proteins encoded by the virus.

Amino Acid Sequence↗
PubMed2006

Intein-mediated reporter gene assay for detecting protein-protein interactions in living mammalian cells.

For nondestructive analysis of chemical processes in living mammalian cells, here we developed a new reporter gene assay for detecting cytosolic protein-protein interactions based on protein splicing of transcription factors with DnaE inteins. The protein splicing induces connection of a DNA-binding protein (modified LexA; mLexA) with a transcription activation domain of a herpes simplex virus protein (VP16AD). We thereby circumvented the limitation of earlier methods for monitoring protein-protein interactions, including the two-hybrid systems, protein complementation systems (PCS), and protein reconstitution systems, and rather combined their advantages. To test the applicability of this method, we monitored epidermal growth factor (EGF)-induced interactions on cell membranes of a known partner, an oncogenic product Ras and its target Raf-1. Ras was connected with N-terminal DnaE and mLexA, while Raf-1 was connected with C-terminal DnaE and VP16AD. Upon stimulation with EGF, the interaction between Ras and Raf-1 triggered folding of the DnaEs, thereby inducing protein splicing to form mLexA-VP16AD fusion protein, and transcription of a reporter gene, firefly luciferase. The extent of Ras-Raf-1 interaction was quantified by measuring the luciferase activity. The interaction was not able to be monitored by two-hybrid systems nor by PCS of split firefly luciferases; however, by using the protein splicing elements and the reporter gene, we obtained the bioluminescence signals sufficient for evaluation of the interactions close to cell membranes.

Animals↗
PubMed1975

Effects of anesthesia, surgery and inflammation upon host defense mechanisms. I. Effects upon the complement system.

Complement protein levels and C7 hemolytic activity were measured in four individuals following anesthesia and surgery, and in a group of 20 patients with inflammatory diseases. Seven of the eight complement components studied characteristically were elevated, most dramatically C1s and C3PA. Elevation of C1s often was greater than elevation of C1q, displaying an independent variation of C1s and C1q in both postoperative and inflammatory disease patient groupds. The major increases of C components were seen subsequent to the peak C-reactive protein response, as was the occurrence of the 'reactor state', a propensity to formation of C56 which surprisingly was associated with increased levels of C7. Levels of properdin frequently were reduced postoperatively. It is concluded that multiple complement components, with the notable exception of properdin, respond as acute phase reactants which are elevated and changed in proportion postoperatively and during inflammatory disease.

Anesthesia, General↗
PubMed1975

Interactions of C-reactive protein with the complement system. II. C-reactive protein-mediated consumption of complement by poly-L-lysine polymers and other polycations.

Cationic homopolymers of poly-L-lysine were found to activate complement (C) via C-reactive protein (CRP) and deplete C3 and C5 as well as early-acting C components. Maximum C consumption was obtained with polymers of 2,000-8,000 daltons; polymers of 1,700, 11,000, and 23,000 daltons were intermediate in reactivity, while L-lysine, lysyl-L-lysine, tetra-L-lysine, and polymers of 70,000-400,000 daltons lacked significant C-consuming activity. Naturally occurring polycations which consumed C in the presence of CRP included myelin basic proteins, cationic proteins of rabbit leukocytes, and both lysine- and arginine-rich histones; poly-L-arginine polymers of 17,000 but not 65,000 daltons also were C-consuming. Polycations without such reactivity included poly-L-orithine (5,000 and 165,000 daltons), egg white and human lysozymes, and Polybrene. The polycations which failed to induce C consumption via CRP, inhibited its consumption by both active polycations and by C-polysaccharide (CPS). The relative inhibitory capacity of phosphorylcholine and polycations in CPS- and polycations-CRP systems was consistent with the concept that phosphate esters and polycations react at the same or an overlapping combining site. The ability of certain polycations to activate C via CRP increases the potential for initiation of host reactions via C. The capacity of other polycations to inhibit C activation via CRP introduces a potential for physiologic or pharmacologic manipulation. These considerations would seem to expand the potential role of CRP in the initiation and modulation of the inflammatory response.

Animals↗
PubMed1988

Biochemical characterization of membrane cofactor protein of the complement system.

Membrane cofactor protein (MCP; formerly termed glycoprotein 45-70 to indicate its Mr) of complement is a widely distributed iC3/C3b binding protein with co-factor activity. On human mononuclear cells and cell lines and platelets, MCP is a doublet. The two forms differ in Mr by approximately 5 k and the upper species is predominant in most individuals. To further characterize these two forms, limited proteolytic digestions were performed. Of the four peptides produced, three have identical Mr indicating that the molecules are similar proteins. Both forms also have acidic isoelectric points and shift to a less acidic isoelectric point after treatment with neuraminidase. Glycosidase digestions indicate that both species contain N- and O-linked oligosaccharides but that the quantity of sialic acid is greater on the larger one. Pulse-chase experiments demonstrate approximately equal quantities of two precursor forms with Mr of 41 and 43 k. These two precursors possess N-linked high-mannose type of oligosaccharides and chase into the mature molecules which have complex sugars. The smaller precursor chases at a slower rate, possibly accounting for the reduced quantity of the smaller form of the mature form of MCP. These experiments indicate that the two forms of MCP are structurally similar and are derived from two distinct precursors. They also suggest that variations in the rate of processing of two intracellular precursors may account for the different quantities of the mature forms of this membrane protein.

Antigens, CD↗
PubMed1993

Expression of CD59, a human complement system regulatory protein, in extraembryonic membranes.

CD59 (leukocyte cluster of differentiation antigen 59), is a phosphatidylinositol glycan-anchored membrane protein that inhibits lysis of cells by terminal complement system components. To further define complement regulatory proteins relevant to pregnancy, this study characterized the expression of CD59 in human extraembryonic membranes. Immunohistology with CD59 monoclonal antibody MEM-43 showed that this molecule was normally present on the apical surface of the syncytiotrophoblast, on extravillous cytotrophoblast, and amniotic epithelium. Immunoblotting confirmed that first and second trimester syncytiotrophoblast microvilli (STM) contained a glycoprotein similar in mass and glycosylation to CD59 from adult cells and tissues. Reactivities of STM with MEM-43 in ELISA were 2- to 6-fold higher than those of kidney, erythrocyte and platelet membranes. Term placental STM from recurrent spontaneous aborting patients after immunotherapy, reacted with MEM-43 in ELISA similarly to STM from normal individuals. Plasmas from pregnant women and umbilical cords had 50% or greater reactivity with MEM-43 than did normal plasmas. CD59 could help protect extraembryonic epithelia from damage by complement in maternal blood and amniotic fluid. The apical location of CD59 reflects the immunological roles and functional polarization of plasma membranes in the syncytiotrophoblast.

Abortion, Spontaneous↗
PubMed1982

Purification and structural studies on the complement-system control protein beta 1H (Factor H).

An efficient procedure for the isolation of the complement-system control protein beta 1H (Factor H) from human plasma was developed. The chemical composition and physical characteristics of the protein were studied, and a sequence of 17 amino acid residues at the N-terminus was determined. Factor H is a single-polypeptide-chain glycoprotein of mol.wt. 155 000 containing 9.3% carbohydrate. Factor H is cleaved by plasma proteinases to a two-chain form. This cleavage can be mimicked by trypsin, and the two-chain form retains fully the C3b-inactivator cofactor activity of Factor H. The proteolytic fragments of Factor H are compared with those of other proteins (C4b-binding protein and erythrocyte C3b-receptor) that act as cofactors for C3b-inactivator.

Amino Acid Sequence↗
PubMed1991

Proteins of the complement system and acute phase reactants in sera of patients with spinal cord injury.

Complement activity was studied in patients with spinal cord transection. In some sera acute phase reactants: haptoglobin, C-reactive proteins, ceruloplasmin, as well as fibrinogen and fibrin degradation products, and immune complexes were monitored. Complement and acute phase reactants are increased in a majority of patients. Continuing inflammation and release of inflammatory mediators could be responsible for poor healing that commonly occurs in spinal cord injury. Urinary tract and other infections are associated with some but not all of the protein abnormalities. These proinflammatory proteins may contribute to the lack of healing of spinal transection.

Acute-Phase Proteins↗
PubMed1985

Complement and clinical intervention.

The nine major components of the complement protein system are normally activated in sequence by antigen-antibody complexes, initiating the inflammatory response. The clinical manifestations arise mainly from the release of histamine, mediated by anaphylatoxin action on mast cells. In rampant infection, this classical pathway is enhanced by further activation of complement C3 through a specific enzyme loop, the alternative pathway. Unfortunately the complexity of the complement system makes it vulnerable to external interference, particularly to man's intervention both through the administration of intravenous "drugs" and by certain surgical procedures. This results in gross systemic activation of complement, particularly C3 giving rise to anaphylactoid shock. More recently, direct activation of complement C5 has been reported, particularly as a result of polytrauma. This has consequences on polymorphonuclear leucocyte behaviour and is likely to be involved in adult respiratory distress syndrome (ARDS). Similarly, excessive activation of C3 may stimulate disseminated intravascular coagulation (DIC) rather than immediate anaphylactoid response. The clinical outcome of complement activation appears to depend upon the rate of activation and its extent, as well as upon the particular component involved. In immediate reactions, complement may be involved in both immune and non-immune activations. Bias to certain pathways is revealed by certain drugs or procedures, and practical methods of evaluating reaction mechanisms are discussed. Despite the high incidence of complement involvement in immediate reactions, there are no useful screening pointers to the patient "at risk". Delayed effects have received little attention. Although C3 conversion is certainly associated with DIC, its predictive value in a clinical trial was not very great.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗