Search results for "Anaphylatoxin"
showing 10 items of 13 documents
C3 Drives Inflammatory Skin Carcinogenesis Independently of C5
2021
Nonmelanoma skin cancer such as cutaneous squamous cell carcinoma (cSCC) is the most common form of cancer and can occur as a consequence of DNA damage to the epithelium by UVR or chemical carcinogens. There is growing evidence that the complement system is involved in cancer immune surveillance; however, its role in cSCC remains unclear. Here, we show that complement genes are expressed in tissue from patients with cSCC, and C3 activation fragments are present in cSCC biopsies, indicating complement activation. Using a range of complement-deficient mice in a two-stage mouse model of chemically-induced cSCC, where a subclinical dose of 7,12-dimethylbenz[a]anthracene causes oncogenic mutatio…
Synthesis of complement by macrophages and modulation of their functions through complement activation.
1983
During the last decade considerable progress has been made to characterize intimate functional links between macrophages, a major cellular component of immunoinflammatory responses, and the complement system representing the major humoral mediator of inflammation. Macrophages of various species and tissue sites have been shown to synthesize and release most of the complement components providing these cells with their own \ldpericellular\rd complement system. Circumstantial evidence for the assembly of both classical and alternative pathway convertases has been adduced. An intricate network of feedback loops involving endogenous and extrinsic factors operates to adjust complement production…
Anaphylatoxin-like molecules generated during complement activation induce a dramatic enhancement of particle uptake in rainbow trout phagocytes.
2004
Here we have identified a serum fraction containing approximately 8-kDa molecules with an unexpected capacity to greatly enhance particle uptake in trout head kidney leukocytes (HKLs). This approximately 8-kDa particle-uptake enhancing fraction (PUEF-8) was purified from complement-activated serum by gel filtration chromatography. Mass spectrometric analysis and reactivity of anti-trout C3-1 and C4 antibodies, indicated the presence of C3a, C4a and C5a molecules in PUEF-8. Using a newly developed flow cytometric assay that measures the capacity of cells to ingest fluorescent beads, we showed that PUEF-8 induced a striking enhancement (344+/-50% higher than the PBS control value) in the numb…
Application of C1-Esterase Inhibitor During Reperfusion of Ischemic Myocardium
2001
Background—Complement activation during reperfusion of ischemic myocardium augments myocardial injury, and complement inhibition with C1-esterase inhibitor (C1-INH) at the time of reperfusion exerts marked cardioprotective effects in experimental studies. Application of C1-INH in newborns, however, was recently reported to have dangerous and even lethal side effects. This study addresses the essential role of dosage in studies using C1-INH.Methods and Results—Cardioprotection by C1-INH was examined in a pig model with 60 minutes of coronary occlusion followed by 120 minutes of reperfusion. C1-INH was administered intravenously 5 to 10 minutes before coronary reperfusion without heparin at a…
Ability of the T cell-replacing polyanion dextran sulfate to trigger the alternate pathway of complement activation.
1973
Dextran sulfate (DS) consumed C3 in C4 deficient guinea pig serum. This temperature-dependent reaction required Mg++ ions and could therefore be blocked by EDTA. Isolated C3 was not influenced by DS, but serum factors were required for C3 consumption. The C3 proactivator as well as C3 were converted to their activated state by DS in guinea pig and human serum, as revealed by immunoelectrophoretical analysis. DS generated anaphylatoxin activity in serum. It is concluded that DS activates C3 via the alternate pathway of complement activation. This potency of the polyanion might serve as a tentative explanation for its T cell-replacing effect in an antibody-forming system, which was reported b…
The Clinical Enzymology of the Complement System
1989
The complement (C) system is one of the most important humoral systems mediating many activities that contribute to inflammation and host defense, e.g. various anaphylatoxin activities, Chemotaxis and opsonization for phagocytosis. The C system is similar to other humoral systems, such as coagulation, fibrinolysis and the kinin system, a multifactoral system whose activation represents sequentially occurring multi-step activation cascades of the “classical” as well as the “alternative” pathway.
Demonstration of High-Affinity Binding Sites for C3a Anaphylatoxin on Guinea-Pig Platelets
1978
3H-serotonin release from guinea-pig platelets was demonstrated to be the consequence of C3a binding to these cells. A Scatchard analysis of dose-response data of the 125I-C3a binding pattern to guinea-pig platelets pointed to the existence of binding sites with high and low affinity for the C3a molecule (HA and LA receptors). HA receptors are specific for C3a with intact C-terminal arginine. whereas C3adesarg only interacts with LA receptors. The release of serotonin may be induced by a combined reaction of C3a with HA receptors and LA receptors on the platelet membrane.
Comparative study on biological activities of various anaphylatoxins (C4a, C3a, C5a)
1981
Several anaphylatoxic substances (human C3a, guinea pig C3a, human C4a, guinea pig C5a, and a synthetic C3a-related hexapeptide) were compared with regard to their ability to induce secretion of [3H] serotonin from guinea pig platelets. Functional identity of the C3a preparations, C4a, and the hexapeptide was demonstrated by the phenomenon of crossed desensitization. Whereas C3a of human and guinea pig origin proved to be qualitatively and quantitatively identical, C4a expressed only 3% of the activity of the C3 fragments on a molar basis. Investigations with goat anti-guinea pig C3a demonstrate that human and guinea pig C3a possess one antigenic determinant in common; however, this determi…
Platelet Activation: a New Biological Activity of Guinea-pig C3a Anaphylatoxin
1978
3H-serotonin-release from labelled gp-platelets is established as a sensitive method for testing a new biological activity of gp-C3a anaphylatoxin in an autologous situation. Time-, dose- and temperature-dependent release reactions as well as specific inhibition by carboxypeptidase B and anti-C3a antibodies show that C3a is a potent and specific inducer of platelet activation. Inactive C3a does not induce 3H-serotonin-release but specifically inhibits the action of C3a on platelets.
Comparative study on biological effects of the guinea pig complement-peptide C3a and C3a-related synthetic oligopeptides
1980
Dose-response experiments with guinea pig C3a and a synthetic hexapeptide (amino acid residues 72–77), representing the COOH-terminal sequence of human C3a, were performed in two recently described bioassay systems for C3a, i.e. cytotoxicity against tumor cells measured as LDH and 51Cr-release and non cytolytic serotonin release from guinea pig platelets. Compared to the classical anaphylatoxic assay (guinea pig ileum contraction), nearly identical reactivities were observed in all three test systems with C3a and, although quantitatively different, with hexapeptide.