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At least 181 records · Page 10Linked to original sources
PubMed1992

Coagulation inhibitors in pulmonary cancer patients.

Pulmonary cancer patients are known to have an elevated risk to suffer from thromboembolic complications. Because hereditary deficiencies of coagulation inhibitors antithrombin III, protein C and protein S are known to cause thromboembolic events it was the aim of our study to search for acquired alterations of these proteins in pulmonary cancer patients. We could demonstrate antithrombin III and protein C to be within the normal range in patients suffering from pulmonary carcinoma. In contrast, in patients suffering from metastatic pulmonary carcinoma bound protein S was increased, while free protein S was significantly reduced. In some patients the decrease of free protein S was comparable to the diminution observed in hereditary protein S deficient patients. A high positive correlation was observed between C4b-binding protein and bound protein S, indicating C4b-binding protein to be a regulatory protein for the shift from free and anticoagulatory active to bound and anticoagulatory inactive protein S. In conclusion, the decrease of free protein S is one source for thromboembolic complications in pulmonary cancer patients. For interpretation of altered free protein S levels it is useful to measure C4b-binding protein.

Aged↗
PubMed2001

Incorporation of decay-accelerating factor into the baculovirus envelope generates complement-resistant gene transfer vectors.

Baculovirus vectors are an efficient means to deliver genes into hepatocytes in vitro. In experiments that exclude components of the complement system, gene transfer is facilitated. Therefore, the complement system has been defined to represent a potent primary barrier to direct application of baculoviruses in vivo. Here we have genetically manipulated baculoviruses so that the complement-regulatory protein human decay- accelerating factor (DAF) is incorporated into the viral envelope. We found that this modification protected baculovirus vectors against complement-mediated inactivation. Complement-resistant baculovirus vectors were additionally analyzed by immunoblotting and electron microscopy, showing the extent of envelope-incorporated DAF and shape of complement-resistant baculoviruses after exposure to complement. This modified baculovirus vector allowed for an enhanced gene transfer into complement-sufficient neonatal rats in vivo, and thus represents a step in the development of improved alternative viral vectors for gene therapy.

Animals↗
PubMed2000

Nonpolar inactivation of the hypervariable streptococcal inhibitor of complement gene (sic) in serotype M1 Streptococcus pyogenes significantly decreases mouse mucosal colonization.

Group A Streptococcus (GAS) is a human pathogen that commonly infects the upper respiratory tract. GAS serotype M1 strains are frequently isolated from human infections and contain the gene encoding the hypervariable streptococcal inhibitor of complement protein (Sic). It was recently shown that Sic variants were rapidly selected on mucosal surfaces in epidemic waves caused by M1 strains, an observation suggesting that Sic participates in host-pathogen interactions on the mucosal surface (N. P. Hoe, K. Nakashima, S. Lukomski, D. Grigsby, M. Liu, P. Kordari, S.-J. Dou, X. Pan, J. Vuopio-Varkila, S. Salmelinna, A. McGeer, D. E. Low, B. Schwartz, A. Schuchat, S. Naidich, D. De Lorenzo, Y.-X. Fu, and J. M. Musser, Nat. Med. 5:924-929, 1999). To test this idea, a new nonpolar mutagenesis method employing a spectinomycin resistance cassette was used to inactivate the sic gene in an M1 GAS strain. The isogenic Sic-negative mutant strain was significantly (P < 0.019) impaired in ability to colonize the mouse mucosal surface after intranasal infection. These results support the hypothesis that the predominance of M1 strains in human infections is related, in part, to a Sic-mediated enhanced colonization ability.

Animals↗
PubMed1976

Inactivator of the first component of human complement (C1INA). Enhancement of C1INA activity against C1s by acidic mucopolysaccharides.

Acidic mucopolysaccharides enhanced C1INA activity against C1s. The presence of heparin in the reaction mixture of C1INA and C1s markedly enhanced the inactivation of C1s by potentiating C1INA activity. Treatment of serum with C1s resulted in the inactivation of C4 hemolytic activity, but this inactivation of C4 by C1s was prevented by the presence of heparin presumably due to the enhancement of C1INA activity normally present in serum. The other acidic mucopolysaccharides, chondroitin sulfates A, B and C, were also effective on potentiating C1INA activity against C1s, but they were less active than heparin. The enhancement of C1INA activity by heparin was not observed in the reaction between C1INA and plasmin.

Chondroitin Sulfates↗
PubMed2001

A novel chicken membrane-associated complement regulatory protein: molecular cloning and functional characterization.

A cDNA encoding a membrane-associated complement (C) regulatory protein was identified here for the first time in an oviparous vertebrate, chicken. This protein, named Cremp, possessed five short consensus repeats (SCRs) and one SCR-like domain followed by a transmembrane domain and a cytoplasmic tail. SCR1/SCR2 of Cremp were 43.6% identical with SCR2/SCR3 of human decay-accelerating factor (CD55), and SCR3/SCR4 were 45.3% identical with those of human membrane cofactor protein (CD46). Cremp is likely to be an ancestral hybrid protein of human decay-accelerating factor and membrane cofactor protein rather than a homolog of rodent C receptor 1-related protein y, which structurally resembles human CR1 (CD35). Chinese hamster ovary cells transfected with Cremp were efficiently protected from chicken C but not from human or rabbit C in both classical and alternative pathways. Thus, chicken Cremp is a membrane C regulator for cell protection against homologous C. Cremp mRNA was seen as a doublet comprised of a faint band of 2.2 kb and a thick band of 3.0 kb on RNA blotting analysis. An Ab against chicken Cremp recognized a single band of 46.8 kDa on immunoblotting. mRNA and protein of Cremp were ubiquitously expressed in all chicken organs tested. Minute amounts of dimer were present in some tissues. Surface expression of Cremp was confirmed by flow cytometry and immunofluorescence analysis. These results suggested that even in nonmammals a C regulatory membrane protein with ubiquitous tissue distribution should be a prerequisite for protection of host cells from homologous C attack.

Amino Acid Sequence↗
PubMed1975

Complement inhibitor(s) released by leukocytes. III. Evidence for a "new" C1 inhibitor in the supernatants of short-term cultures of mouse spleen and thymus cells.

Mouse spleen or thymus cells in short-term culture release a factor, designated S, that binds to sheep erythrocytes (E). Supernatant-treated sheep erythrocytes (SE) are capable of fixing and transferring the activated first component of guinea pig complement. SEC1, however is not capable of initiating hemolysis by the rest of the complement components. SE is capable of binding but not activating native C1; native C1 bound to SE seems irreversibly inhibited. Evidence is presented that S may be the same factor as the previously described inhibitor released by mouse spleen or thymus cells that inhibits the utilization of C2 by EAC14.

Animals↗
PubMed1992

Monoclonal antibody-based enzyme-linked immunosorbent assays (ELISA) for the measurement of vitamin K-dependent protein S: the effect of antibody immunoreactivity on plasma protein S antigen determinations.

Two monoclonal antibodies (Mabs) specifically directed to human protein S (PS) - named 5E9E9 and 3B10.25 - were produced and their properties compared to those of 2 previously characterized anti-PS-Mabs (HPS-2 and S10). 3B10.25, similar to S10, was directed to the calcium-free conformation of PS and had virtually identical affinity for free and C4b-binding protein (C4b-BP)-bound PS; 5E9E9 similar to HPS-2, had no calcium-dependency and was selectively directed to free PS. All Mabs were equally reactive to freshly purified and thrombin-cleaved PS. To evaluate the influence of C4b-BP bound PS on PS antigen determinations, ELISA systems employing the four Mabs individually as capture antibody (Ab) and peroxidase-conjugated polyclonal anti-PS IgG as detecting Ab were developed and compared to immunoelectrophoresis (EIA) and to an ELISA employing polyclonal anti-PS IgG as capture and detecting Ab, in the determination of PS in purified systems and in plasma. With all the ELISAs there was parallelism of dilution curves obtained with normal plasma and purified PS; however, supplementation of plasma with purified C4b-BP resulted in loss of parallelism when employing the Mabs directed to free PS as capture Ab. Influence of high C4b-BP on PS antigen determinations was confirmed in a series of plasma samples from patients with C4b-BP levels ranging from 70% to over 200%. Compared to the values obtained with the S10- or 3B10.25 - based ELISAs - which were similar despite a 10-fold difference in sample dilution - plasma PS was underestimated by the ELISAs employing 5E9E9 or HPS-2 while it was overestimated by EIA.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1989

Factor J: isolation and characterization of a new polypeptide inhibitor of complement C1.

An Mr 20,000 protein inhibitor of C1, the first component of complement, has been purified from human urine and characterized. This inhibitor, tentatively designated factor J, is apparently distinct from known complement inhibitors. During purification on QAE-Sephadex, Mono Q, and heparin-Sepharose, factor J was detected by its ability to inhibit the complement-mediated lysis of sheep erythrocytes bearing antibody, C1, and activated C4 (EAC14). The purity of factor J was documented by the concordant elution from a hydroxylapatite column of functional activity and the UV absorbance as measured at three different wavelengths (220, 254, and 280 nm). The relative Mr of 20,000 was determined by sodium dodecyl sulfate-slab gel electrophoresis of radioiodinated protein. Amino acid analysis indicated a high cysteine content and allowed calculations of a specific activity of 7 functional units/pmol. The target of factor J inhibitory activity on the lysis of EAC14 was localized to C1 by the following criteria: factor J inhibited C1 in a C1 transfer assay, but had no effect on C42 activity or decay, and had no effect on the efficiency of isolated C2 or C3-C9 as provided in serum-EDTA. Factor J inhibition was rapid and not significantly influenced by temperature. In a second functional assay, factor J inhibited the association of the tetrameric complex C1r2s2 with 125I-C1q, and the results, when analyzed graphically by a reciprocal plot, were consistent with noncompetitive inhibition (Ki = 529-760 pM range). Functional and/or antigenic data indicated that factor J is distinct from the other known inhibitors of C1, namely the C1 inhibitor and the C1q inhibitor. Antihuman serum precipitated radioiodinated factor J, indicating that an antigen identical or cross-reacting with factor J exists in serum. In summary, factor J is a newly described potent inhibitor of C1 function.

Animals↗
PubMed1976

Leukocyte-derived complement inhibitor. IV. The functional properties of C1 bound to erythrocytes pretreated with leukocyte culture supernatant.

E, pretreated with leukocyte cultures supernatant (ES), binds C1 through C1q; ES and EIgM that bind the same amount of C1 as measured in a hemolytic assay have the same uptake of 125I-C1q; ESC1q and EIgMC1q, carrying the same number of molecules of CUq per cell, have the same uptake of CUr and CUs; soluble immune compleses prevent the binding of C1 and C1q to ES. The activity of C1 bound to ES is impaired; ESC1 can react with C4 but not with C2. The C4 turnover and the C1 ING turnover by ESC1 are reduced so that ES-bound C1 is protected from destruction by C1 ING. These modifications are fully reversed when C1 is transferred from ES to EA:C1 recovers its ability to react with C2, and C1 INH. Thus the C1s activity can be modulated inside the C1 molecular complex upon binding of C1q to a lymphocyte product. In addition, the 125I-C1q uptake is proportional to the amount of IgM hemolysin used to sensitize E; it has, however, an exponential relationship to the amount of IgG or S used to sensitize E. The ratio of 125I-C1q uptake towhole C1 uptake measured in a hemolytic assay is lowerthan 2. This indicates that one molecule of IgM is sufficient to bind one molecule of C1q on E, that several molecules of IgG or S are required to bind one molecule of C1q, and that one molecule of C1q is sufficient to create a lytic site on E.

Animals↗
PubMed1999

Protection of MLV vector particles from human complement.

Murine cell-derived MLV vector particles usually are highly sensitive to human complement-mediated lysis. Expression of the human complement inhibitor CD59 on murine packaging cells resulted in partial protection of these cells from lysis caused by human complement proteins. Furthermore, CD59 was incorporated into MLV vector particles released by these packaging cells, leading to an improved resistance of the virions against human complement-mediated inactivation.

Animals↗
PubMed1986

Differential interaction of the C3b/C4b receptor and MHC class I with the cytoskeleton of human neutrophils.

As measured by fluorescence microscopy and radioligand binding, C3b/C4b receptors (CR1) became attached to the detergent-insoluble cytoskeleton of human neutrophils when receptors were cross-linked by affinity-purified polyclonal F(ab')2 anti-CR1, dimeric C3b, or Fab monoclonal anti-CR1 followed by F(ab')2 goat anti-mouse F(ab')2. CR1 on neutrophils bearing monovalent anti-CR1 was not attached to the cytoskeleton. In contrast, cross-linked CR1 on erythrocytes and cross-linked MHC Class I on neutrophils were not cytoskeleton associated. A possible role for filamentous actin (F-actin) in the binding of cross-linked CR1 to neutrophil cytoskeleton was suggested by three observations. When neutrophils were differentially extracted with either Low Salt-detergent buffer or High Salt-detergent buffer, stained with FITC-phalloidin, and examined by fluorescent flow cytometry, the residual cytoskeletons generated with the former buffer were shown to contain polymerized F-actin, whereas cytoskeletons generated with the latter buffer were found to be depleted of F-actin. In parallel experiments, High Salt-detergent buffer was also found to release cross-linked CR1 from neutrophils. Second, depolymerization of F-actin by DNAse I released half of the cytoskeletal-associated cross-linked CR1. Third, immunoadsorbed neutrophil CR1, but not MHC Class I or erythrocyte CR1, specifically bound soluble 125I-actin. In addition, Fc receptor and CR3, other phagocytic membrane proteins of neutrophils, specifically bound 125I-actin. These data demonstrate that CR1 cross-linked on neutrophils becomes associated with detergent-insoluble cytoskeleton and that this interaction is mediated either directly or indirectly by actin.

Actins↗