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  • 1
    Electronic Resource
    Electronic Resource
    Generation of Anaphylatoxin Activity Related to C3a, by Treatment of Human Serum with the Nitrogen Nucleophile N2H4 or the Chaotrope KSCN (1985)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 22 (1985), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The present study is concerned with the proteolytic processing of complement component C3 in normal human serum treated with N2M4 or KSCN in the presence of EDTA. Upon incubation with these agents. C3 is first converted to the thiolester-cleaved form (C3i) and thereafter fragmented by factor I. In consecutive, relatively slow steps, spasmogenic and platelet-aggregating activity is released. The active principle shows characteristics of C3a. First, the pretreated sera deactivate guinea pig ileum and platelets towards the action of C3ahog, but not C5a-desArghog. Second, the activity is only stable under conditions causing inhibition of serum carboxypeptidase N. such as in the presence of EDTA or of MERGETPA (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid). Third, the molecular weight deter mined by gel filtration is in agreement with that of C3a. The release of C3a activity requires conversion of C3 to C3i, as well as the complement-independent generation of proteolytic activity in the pretreated sera. The enzyme releasing C3a activity is a serine esterase probably identical with Hageman factor, kallikrein, or another protease related to the contact system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1985.tb01926.x
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  • 2
    Electronic Resource
    Electronic Resource
    Isolation and Properties of a Complement Inhibitor from Naja haje Venom, Distinct from Known Anticomplementary Factors in Cobra Venom (1981)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 14 (1981), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A complement inhibitor (CI) has been isolated from cobra (Naja haje) venom which is distinct from the two known anticomplementary factors in cobra venom [1], in functional properties as well as structure. CI is a small (mol. wt 26,000, determined by sodium dodecyl sulphate gel electrophoresis), heat-labile glycoprotein; the amino acid composition is that of a globular protein. CI interferes at various steps of the complement sequence, including reactions of the classical and the alternative pathway. No effect was observed on C4 fixation and on the assembly of the membrane attack complex from C6–9 (minor inhibiting effects, if present, have not been excluded). Initiation of the alternative pathway is inhibited by CI already at the stage of cleavage of factor B. CI binds to C4, C4b. C3 and C3b: since the major inhibitory action of CI is lost after washing of cell intermediates, complex formation and, as a consequence, steric hindrance may be responsible for the inhibiting effects of CI. CI also interferes with binding of C3b to C3b receptors on human erythrocytes. CI is non-toxic in mice when given intraperitoneally in doses of 5 μg/g.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1981.tb00190.x
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  • 3
    Electronic Resource
    Electronic Resource
    Biological properties of dihydro-leukotriene B"4, an alternative leukotriene B"4 metabolite
    Amsterdam : Elsevier
    FEBS Letters 231 (1988), S. 385-388 
    Details
    ISSN: 0014-5793
    Keywords: (Leukocyte) ; Chemotaxis ; Dihydro-leukotriene B"4 ; Leukotriene B"4 ; Leukotriene metabolism ; Oxidative burst
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0014-5793(88)80855-X
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  • 4
    Electronic Resource
    Electronic Resource
    Induction of platelet aggregation by the complement-derived peptides C3a and C5a (1976)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 295 (1976), S. 71-76 
    Details
    ISSN: 1432-1912
    Keywords: Platelet aggregation ; Peptides ; Complement system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of two complement-derived peptides, hog serum C3a and C5a, on platelet aggregation in platelet-rich plasma and suspensions in Tyrode solution was investigated. 1. Guinea-pig platelets were aggregated by both C3a and C5a; the spasmogenically inactive product of C3a, C3ai, also induced aggregation. Threshold concentrations were in the range of 10−6–10−9 M depending on the peptide and platelet preparation. 2. Cat platelets were aggregated by C5a (threshold concentrations 10−7–10−8 M) but not by C3a. 3. Platelets from pig, rabbit and man were not aggregated by either of the two peptides in concentrations of up to 5x10−6 M. 4. When C5a was administered repeatedly in subthreshold doses guinea-pig platelets became tachyphylactic to C5a but were still aggregable by C3a or ADP. Conversely, platelets desensitized to C3a still reacted to C5a or ADP. Tachyphylaxis towards C5a developed also when platelets were incubated with C5a in the absence of free Ca2+ under which condition they do not react. The tachyphylaxis in this case became evident after recalcification of the medium. The lack of cross-desensitization indicates that C3a and C5a react via different receptors. 5. C3a and C5a were injected i.v. into guinea pigs. Histological examination of the lungs revealed that some of the smaller vessels (20–30 μ in diameter) were occluded by platelet aggregates. In addition signs of severe acute emphysema were seen in animals treated with C5a, but only slight emphysema in C3a-treated animals. Intravenous injections of C3a into guinea pigs caused but weak respiratory distress and drowsiness and never killed an animal (at doses of up to 20 mg per kg body weight), whereas C5a caused the well-known severe respiratory failure and death already at doses of 0.03 mg/kg body weight.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00509775
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of hog anaphylatoxin (C5a) on vascular permeability and leukocyte emigration in vivo (1976)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 295 (1976), S. 237-241 
    Details
    ISSN: 1432-1912
    Keywords: Anaphylatoxin (C5a) ; Chemotaxis ; Leukocytes ; Vascular permeability ; Evans blue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of highly purified hog anaphylatoxin (C5a) in leukocyte emigration were investigated in guinea pigs in vivo using two experimental models: 1. Subcutaneous infusions. Sterile solutions of C5a in saline infused at a rate of 1.8 μg C5a/h (0.2 ml/h) for 10h induced a dense accumulation of leukocytes, mainly neutrophils but also some eosinophils at the site of application. In control infusions with saline alone comparatively few leukocytes were found. 2. Single injections into the pleural cavity. 10 or 20 μg C5a (dissolved in 2 ml saline) caused a dosedependent increase in leukocyte number and volume of pleural exudate. Bradykinin in a dose of 18 μg produced similar fluid exudation as 20 μg C5a but had no significant effect on leukocyte accumulation. Intrapleural injections of C5a further caused the appearance of i.v. injected Evans blue in the pleural cavity. This effect, indicating an increase in vascular permeability lasted for about 3 h. Since at least one of the two models used — subcutaneous infusion—simulates natural conditions—continuous local generation of C5a in small amounts at the site of an inflammatory lesion—the results indicate that C5a once formed by complement activation in natural defense reactions may contribute to local increase in vascular permeability and leukocyte infiltration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00505092
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of the cleavage peptides, C3a and C3ai, from the third component of hog complement on leukocyte accumulation and vascular permeability in vivo (1978)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 302 (1978), S. 45-50 
    Details
    ISSN: 1432-1912
    Keywords: Complement peptides ; Leukocytes ; Chemotaxis ; Vascular permeability ; Desensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of the spasmogenically active cleavage peptide from the third component of complement, C3a, and its spasmogenically inactive derivative, C3ai, on local leukocyte accumulation and vascular permeability in guinea pigs have been studied. 1. After intrapleural injection of 50, 100 or 150 μg both peptides induced a dose-dependent accumulation of leukocytes in the pleural cavity. This effect was significantly (P〈0.05) inhibited by colchicine (0.4 and 2.0 mg/kg), whereas pheniramine (5 mg/kg) and paramethasone (1 mg/kg) showed a slight inhibitory effect only. Indometacin (10 mg/kg) did not affect leukocyte accumulation. 2. C3a and C3ai also increased vascular permeability as shown by extravasation of i.v. applied Evans blue into the pleural cavity. This was partly inhibited by paramethasone and indometacin; pheniramine and colchicine were not inhibitory. When C3ai was injected intrapleurally (once 150 μg) and in addition intravenously (doses of 20, 100 and 150 μg injected every 20 min throughout the experiment), the accumulation of leukocytes in the pleural cavity was markedly decreased, whereas the extravasation of Evans blue was even increased. The inhibition of chemotaxis appears to be due to desensitization of the circulating leukocytes by the intravenously given C3ai thus rendering them unresponsive to the local stimulus of intrapleural C3ai. I.v. given C3ai induced a pronounced increase of the concentration of peripheral leukocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00586595
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  • 7
    Electronic Resource
    Electronic Resource
    Differences in binding of the direct lytic factor (DLF) of cobra venom (Naja naja) to intact red cells and ghosts (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 280 (1973), S. 201-207 
    Details
    ISSN: 1432-1912
    Keywords: Direct Lytic Factor ; Cobra Venom ; Red Cells ; Membranes ; Haemolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The binding of direct lytic factor (DLF) from cobra venom (Naja naja) to intact guinea-pig red cells and to guinea-pig ghosts was estimated quantitatively by bioassay of DLF in the supernatant. 1. DLF was not bound to intact red cells in considerable amounts, during 320 min incubation. 2. The degree of binding to ghosts was much larger than that in suspensions of intact red cells. Binding to ghosts increased with time. 3. Whereas the binding of DLF to ghosts was not much influenced by varying the incubation temperature, its haemolytic activity was completely absent at temperatures below 15°C. By an immunofluorescence technique binding of DLF to erythrocytes was studied morphologically: 1. DLF was only bound to red cell ghosts (guinea pig and rat), but not to intact red cells. This binding was not temperature dependent. 2. Pretreatment of ghosts with SH-reagents such as NEM or PCMB did not prevent binding of DLF. 3. Ghosts prepared by different methods (hypotonic shock, freezing and thawing, ultrasonication, and resealing) were all able to bind DLF to their surface. It is concluded that the binding of small amounts of DLF to intact red cells, observed by bioassay, was due to the presence of a small fraction of lysed cells, and that the binding to ghosts is not related to the lytic effect of DLF but secondary to lysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499181
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  • 8
    Electronic Resource
    Electronic Resource
    Chemotactic effects of the complement-derived peptides C3a, C3ai and C5a (classical anaphylatoxin) on rabbit and guinea-pig polymorphonuclear leukocytes (1978)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 305 (1978), S. 181-184 
    Details
    ISSN: 1432-1912
    Keywords: Chemotaxis ; Complement peptides ; Anaphylatoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The complement-derived peptides C3a, C3ai and C5a (= classical anaphylatoxin) were purified from hog serum and examined for chemotactic activity on rabbit and guinea-pig polymorphonuclear leukocytes (PMN) with the Boyden chamber technique (with filters of 3,0 μm pore size). When media containing albumin or serum were used all peptides induced chemotaxis of both cell species. Only C3a showed a pronounced species dependence in that it was much more active on rabbit than on guinea-pig PMN. No gross differences were found between the influence of 0.5% BSA and 10% heated (56°, 30 min) homologous serum added to the medium. In the absence of protein chemotaxis did not occur.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508290
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  • 9
    Electronic Resource
    Electronic Resource
    Osmotic and non-osmotic components of the haemolysis induced by the direct lytic factor (DLF) of cobra venom (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 282 (1974), S. 255-260 
    Details
    ISSN: 1432-1912
    Keywords: Direct Lytic Factor ; Cobra Venom ; Phospholipase A ; Red Cells ; Haemolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of increasing the (colloid-)osmotic pressure in the extracellular medium on haemolysis by the direct lytic factor of cobra venom (DLF) and phospholipase A has been investigated. For comparison, N-ethyl-maleimide (NEM) and p-chloromercuribenzoate (p-CMB) were used. Dextran and sucrose abolished the haemolytic effect of NEM and p-CMB but reduced only slightly (dextran) or not (sucrose) the weak lytic activity of DLF. Haemolysis by phospholipase A in the presence of DLF, NEM or p-CMB was not significantly inhibited. Hypertonic NaCl solution considerably retarded the onset of haemolysis by DLF plus phospholipase A. The mean corpuscular volume of guinea-pig red cells increased slightly but definitely during incubation with DLF. It is concluded that the haemolytic effect of DLF has non-osmotic as well as osmotic components, and that phospholipase A causes non-osmotic haemolysis. The retardation of haemolysis by hypertonic NaCl probably indicates specific inhibition of bee venom phospholipase A2, not protection of the erythrocytes from osmotic stress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501234
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  • 10
    Electronic Resource
    Electronic Resource
    Histamine release, formation of prostaglandin-like activity (SRS-C) and mast cell degranulation by the direct lytic factor (DLF) and phospholipase A of cobra venom (1975)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 141-156 
    Details
    ISSN: 1432-1912
    Keywords: Histamine ; Prostaglandin ; Mast Cells ; Cobra Venom ; Phospholipase A ; Direct Lytic Factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of Direct Lytic Factor (DLF) and phospholipase A (ph-ase A) from cobra venom, alone and in combination, on mast cell degranulation, histamine release and formation of prostaglandin-like activity (SRS-C) was studied in perfused guinea-pig lungs and in mast cell-containing rat peritoneal cell suspensions. For comparison, the effect of equivalent doses of whole cobra venom was investigated. 1. Cobra venom caused mast cell degranulation, histamine release and SRS-C formation in both systems. For comparable effects much higher doses had to be used in guinea-pig lungs than in rat peritoneal cell suspensions. 2. Ph-ase A showed little degranulation of mast cells in both systems, a limited histamine release in rat peritoneal cell suspensions and none in perfused guinea-pig lungs. It caused a considerable SRS-C formation in both, lung tissue and peritoneal cell suspensions. 3. DLF caused histamine release, SRS-C formation and mast cell degranulation in both systems; in rat peritoneal cell suspensions it acted almost as strong as equivalent doses of cobra venom, in guinea pig lungs it was much less active. 4. In rat peritoneal cell suspensions the effects of DLF and ph-ase A in combination did not exceed the sum of their single effects. In guinea-pig lungs these two substances interacted in a potentiating synergism. It is concluded that DLF is the main cytotoxic principle of cobra venom, whereas ph-ase A alone is not cytotoxic. The difference in the synergism of DLF and ph-ase A between rat peritoneal cells and guinea-pig lungs may be due to two different actions of DLF and species differences as regards sensitivity against these actions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00510446
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