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.
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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.
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2.
Cat platelets were aggregated by C5a (threshold concentrations 10−7–10−8 M) but not by C3a.
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3.
Platelets from pig, rabbit and man were not aggregated by either of the two peptides in concentrations of up to 5x10−6 M.
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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.
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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.
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Abbreviations
- C3a, C5a:
-
cleavage peptides derived from the third and fifth component of complement respectively
- C3ai :
-
Spasmogenically inactive form of C3a resulting from C3a inactivation by carboxypeptidase B
- ADP:
-
Adenosine diphosphate
- PRP:
-
Platelet-rich plasma
- EDTA:
-
Ethylenediamine tetraacetic acid used as disodium salt
References
Becker, E. L., Henson, P. M.: In vitro studies of immunologically induced secretion of mediators from cells and related phenomena. Advanc. Immunol. 17, 93–193 (1973)
Benner, K. U., Schumacher, K.-A., Classen, H.-G.: Platelet aggregation induced by anaphylatoxin and its inhibition. Drug Res. 25, 1635–1638 (1975)
Bettex-Galland, M., Lüscher, E. F., Simon, G., Vassalli, P.: Induction of viscous metamorphosis in human blood platelets by means other than by thrombin. Nature (Lond.) 200, 1109–1110 (1963)
Bodammer, G.: Untersuchungen über den Mechanismus der Blutdruckwirkung des Anaphylatoxins bei Katzen und Meerschweinchen. Naunyn-Schmiedeberg's Arch. Pharmak. exp. Path. 262, 197–207 (1969)
Born, G. V. R.: Quantitative investigations into the aggregation of blood platelets. J. Physiol. (Lond.) 162, 67P (1962)
Dale, H. H., Kellaway, C. H.: Anaphylaxis and anaphylatoxins. Phil. Trans. B 211, 273–315 (1922)
Dodds, W. J., Pickering, R. J.: Purified cobra venom factor: Effect on blood platelets. Proc. Soc. exp. Biol. (N. Y.) 140, 429–434 (1972)
Giertz, H., Hahn, F.: Anaphylatoxin. In: Histamine and Anti-Histaminics. Handb. d. exp. Pharmakol., Vol. XVIII/1 (O. Eichler and A. Farah, eds.), pp. 517–568. Berlin-Heidelberg-New York: Springer 1966
Giertz, H., Hahn, F., Jurna, I., Schmutzler, W.: Vergleichende Untersuchungen über den anaphylaktischen Schock und den Anaphylatoxinschock an intakten Meerschweinchen. Naunyn-Schmiedeberg's Arch. exp. Path. Pharmak. 242, 65–75 (1961)
Gröttum, K. A.: Platelet surface charge and aggregation. Effect of polyelectrolytes. Thromb. Diathes. haemorrh. (Suttg.) 21, 450–462 (1969)
Henson, P. M., Cochrane, C. G.: Immunological induction of increased vascular permeability. II. Two mechanisms of histamine release from rabbit platelets involving complement. J. exp. Med. 129, 167–184 (1969)
Liefländer, M., Dielenberg, D., Schmidt, G., Vogt, W.: Structural elements of anaphylatoxin obtained by contact activation of hog serum. Hoppe-Seylers Z. physiol. Chem. 353, 385–392 (1972)
Marney, S. R.: Rabbit platelet injury by soluble antigen and antibody. II. Platelet aggregation in heparinized plasma and citrated plasma, relationship to ADP and inhibition by cobra factor. J. Immunol. 106, 82–90 (1971)
Mueller-Eckhardt, Ch., Lüscher, E. F.: Immune reactions of human blood platelets. I. A comparative study on the effects on platelets of heterologous antiplatelet antiserum, antigen-antibody-complexes, aggregated gammaglobulin and thrombin. Thromb. Diathes. haemorrh. (Stuttg.) 20, 155–167 (1968a)
Mueller-Eckhardt, Ch., Lüscher, E. F.: Immune reactions of human blood platelets. II. The effect of latex particles coated with gammaglobulin in relation to complement activation. Thromb. Diathes. haemorrh. (Stuttg.) 20, 168–179 (1968b)
Pfueller, S. L., Lüscher, E. F.: The effects of immune complexes on blood platelets and their relationship to complement activation. Immunochemistry 9, 1151–1165 (1972)
Pfueller, S. L., Lüscher, E. F.: Studies on the mechanisms of the human platelet release reaction induced by immunologic stimuli. II. Effects of zymosan. J. Immunol. 112, 1211–1218 (1974)
Schumacher, K. A., Classen, H. G., Hagedorn, M., Benner, K. U., Späth, M., Mittermayer, Ch.: Effects of anaphylatoxin plasma in cats: Hemodynamic changes induced by platelet aggregation. Drug. Res. 24, 122–126 (1974)
Siraganian, R. P., Sandberg, A. L., Alexander, A., Osler, A. G.: Platelet injury due to activation of the alternate complement pathway. J. Immunol. 110, 490–497 (1973)
Vallota, E. H., Müller-Eberhard, H. J.: Formation of C3a and C5a anaphylatoxins in whole human serum after inhibition of the anaphylatoxin inactivator. J. exp. Med. 137, 1109–1123 (1973)
Vogt, W.: Preparation and some properties of anaphylatoxin from hog serum. Biochem. Pharmacol. 17, 727–733 (1968)
Zucker, M. B., Grant, R. A.: Aggregation and release reaction induced in human blood platelets by zymosan. J. Immunol. 112, 1219–1230 (1974)
Zucker, M. B., Grant, R. A., Alper, C. A., Goodkofsky, I. Lepow, I. H.: Requirement for complement components and fibrinogen in the zymosan induced release reaction of human blood platelets. J. Immunol. 113, 1744–1751 (1974)
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Grossklaus, C., Damerau, B., Lemgo, E. et al. Induction of platelet aggregation by the complement-derived peptides C3a and C5a. Naunyn-Schmiedeberg's Arch. Pharmacol. 295, 71–76 (1976). https://doi.org/10.1007/BF00509775
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DOI: https://doi.org/10.1007/BF00509775