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  • 1
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Platelet aggregation ; Peptides ; Complement system
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00509775
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  • 2
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Anaphylatoxin (C5a) ; Chemotaxis ; Leukocytes ; Vascular permeability ; Evans blue
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00505092
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  • 3
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Complement peptides ; Leukocytes ; Chemotaxis ; Vascular permeability ; Desensitization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00586595
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  • 4
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Chemotaxis ; Complement peptides ; Anaphylatoxin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00508290
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  • 5
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Histamine ; Prostaglandin ; Mast Cells ; Cobra Venom ; Phospholipase A ; Direct Lytic Factor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00510446
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