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. 1995 Feb;114(3):578–583. doi: 10.1111/j.1476-5381.1995.tb17178.x

Inhibition of carrageenin-induced rat paw oedema by crotapotin, a polypeptide complexed with phospholipase A2.

E C Landucci 1, E Antunes 1, J L Donato 1, R Faro 1, S Hyslop 1, S Marangoni 1, B Oliveira 1, G Cirino 1, G de Nucci 1
PMCID: PMC1510024  PMID: 7537590

Abstract

1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micrograms/paw) in the rat hind-paw. The effects of crotapotin on platelet aggregation, mast cell degranulation and eicosanoid release from guinea-pig isolated lung were also investigated. 2. Subplantar co-injection of crotapotin (1 and 10 micrograms/paw) with carrageenin or injection of crotapotin (10 micrograms/paw) into the contralateral paw significantly inhibited the carrageenin-induced oedema. This inhibition was also observed when crotapotin (10-30 micrograms/paw) was administered either intraperitoneally or orally. Subplantar injection of heated crotapotin (15 min at 60 degrees C) failed to inhibit carrageenin-induced oedema. Subplantar injection of crotapotin (10 micrograms/paw) also significantly inhibited the rat paw oedema induced by compound 48/80, but it did not affect 5-HT-induced oedema. 3. In adrenalectomized animals, subplantar injection of crotapotin markedly inhibited the oedema induced by carrageenin. The inhibitory effect of crotapotin was also observed in rats depleted of histamine and 5-HT stores. 4. Crotapotin (30 micrograms/paw) had no effect on either the histamine release induced by compound 48/80 in vitro or on the platelet aggregation induced by both arachidonic acid (1 nM) and platelet activating factor (1 microM) in human platelet-rich plasma. The platelet aggregation and thromboxane B2 (TXB2) release induced by thrombin (100 mu ml-1) in washed human platelets were also not affected by crotapotin.(ABSTRACT TRUNCATED AT 250 WORDS)

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  1. BORN G. V., CROSS M. J. THE AGGREGATION OF BLOOD PLATELETS. J Physiol. 1963 Aug;168:178–195. doi: 10.1113/jphysiol.1963.sp007185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bakhle Y. S., Moncada S., de Nucci G., Salmon J. A. Differential release of eicosanoids by bradykinin, arachidonic acid and calcium ionophore A23187 in guinea-pig isolated perfused lung. Br J Pharmacol. 1985 Sep;86(1):55–62. doi: 10.1111/j.1476-5381.1985.tb09434.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berg O. G., Yu B. Z., Rogers J., Jain M. K. Interfacial catalysis by phospholipase A2: determination of the interfacial kinetic rate constants. Biochemistry. 1991 Jul 23;30(29):7283–7297. doi: 10.1021/bi00243a034. [DOI] [PubMed] [Google Scholar]
  4. Bon C., Changeux J. P., Jeng T. W., Fraenkel-Conrat H. Postsynaptic effects of crotoxin and of its isolated subunits. Eur J Biochem. 1979 Sep;99(3):471–481. doi: 10.1111/j.1432-1033.1979.tb13278.x. [DOI] [PubMed] [Google Scholar]
  5. Bon C. Synergism of the two subunits of crotoxin. Toxicon. 1982;20(1):105–109. doi: 10.1016/0041-0101(82)90173-8. [DOI] [PubMed] [Google Scholar]
  6. Bouchier C., Boulain J. C., Bon C., Ménez A. Analysis of cDNAs encoding the two subunits of crotoxin, a phospholipase A2 neurotoxin from rattlesnake venom: the acidic non enzymatic subunit derives from a phospholipase A2-like precursor. Biochim Biophys Acta. 1991 Mar 26;1088(3):401–408. doi: 10.1016/0167-4781(91)90132-6. [DOI] [PubMed] [Google Scholar]
  7. Brazil O. V. Pharmacology of crystalline crotoxin. II. Neuromuscular blocking action. Mem Inst Butantan. 1966;33(3):981–992. [PubMed] [Google Scholar]
  8. Cabré F., Moreno J. J., Carabaza A., Ortega E., Mauleón D., Carganico G. Antiflammins. Anti-inflammatory activity and effect on human phospholipase A2. Biochem Pharmacol. 1992 Aug 4;44(3):519–525. doi: 10.1016/0006-2952(92)90444-n. [DOI] [PubMed] [Google Scholar]
  9. Chiu H. F., Burrall B. A. Effect of interleukin 3 on the differentiation and histamine content of cultured bone marrow mast cells. Agents Actions. 1990 Nov;31(3-4):197–203. doi: 10.1007/BF01997608. [DOI] [PubMed] [Google Scholar]
  10. Choumet V., Saliou B., Fideler L., Chen Y. C., Gubensek F., Bon C., Delot E. Snake-venom phospholipase A2 neurotoxins. Potentiation of a single-chain neurotoxin by the chaperon subunit of a two-component neurotoxin. Eur J Biochem. 1993 Jan 15;211(1-2):57–62. doi: 10.1111/j.1432-1033.1993.tb19869.x. [DOI] [PubMed] [Google Scholar]
  11. Cirino G., Peers S. H., Flower R. J., Browning J. L., Pepinsky R. B. Human recombinant lipocortin 1 has acute local anti-inflammatory properties in the rat paw edema test. Proc Natl Acad Sci U S A. 1989 May;86(9):3428–3432. doi: 10.1073/pnas.86.9.3428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Di Rosa M., Giroud J. P., Willoughby D. A. Studies on the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J Pathol. 1971 May;104(1):15–29. doi: 10.1002/path.1711040103. [DOI] [PubMed] [Google Scholar]
  13. Flower R. J., Blackwell G. J. The importance of phospholipase-A2 in prostaglandin biosynthesis. Biochem Pharmacol. 1976 Feb 1;25(3):285–291. doi: 10.1016/0006-2952(76)90216-1. [DOI] [PubMed] [Google Scholar]
  14. Flower R. J. Eleventh Gaddum memorial lecture. Lipocortin and the mechanism of action of the glucocorticoids. Br J Pharmacol. 1988 Aug;94(4):987–1015. doi: 10.1111/j.1476-5381.1988.tb11614.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Flower R. J., Parente L., Persico P., Salmon J. A. A comparison of the acute inflammatory response in adrenalectomised and sham-operated rats. Br J Pharmacol. 1986 Jan;87(1):57–62. doi: 10.1111/j.1476-5381.1986.tb10156.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Franson R., Dobrow R., Weiss J., Elsbach P., Weglicki W. B. Isolation and characterization of a phospholipase A2 from an inflammatory exudate. J Lipid Res. 1978 Jan;19(1):18–23. [PubMed] [Google Scholar]
  17. Gopalakrishnakone P., Dempster D. W., Hawgood B. J., Elder H. Y. Cellular and mitochondrial changes induced in the structure of murine skeletal muscle by crotoxin, a neurotoxic phospholipase A2 complex. Toxicon. 1984;22(1):85–98. doi: 10.1016/0041-0101(84)90141-7. [DOI] [PubMed] [Google Scholar]
  18. Green J. A., Smith G. M., Buchta R., Lee R., Ho K. Y., Rajkovic I. A., Scott K. F. Circulating phospholipase A2 activity associated with sepsis and septic shock is indistinguishable from that associated with rheumatoid arthritis. Inflammation. 1991 Oct;15(5):355–367. doi: 10.1007/BF00917352. [DOI] [PubMed] [Google Scholar]
  19. Habermann E., Breithaupt H. Mini-review. The crotoxin complex--an example of biochemical and pharmacological protein complementation. Toxicon. 1978;16(1):19–30. doi: 10.1016/0041-0101(78)90056-9. [DOI] [PubMed] [Google Scholar]
  20. Jain M. K., Yu B. Z., Rogers J., Ranadive G. N., Berg O. G. Interfacial catalysis by phospholipase A2: dissociation constants for calcium, substrate, products, and competitive inhibitors. Biochemistry. 1991 Jul 23;30(29):7306–7317. doi: 10.1021/bi00243a036. [DOI] [PubMed] [Google Scholar]
  21. Landucci E. C., Condino-Neto A., Perez A. C., Hyslop S., Corrado A. P., Novello J. C., Marangoni S., Oliveira B., Antunes E., de Nucci G. Crotoxin induces aggregation of human washed platelets. Toxicon. 1994 Feb;32(2):217–226. doi: 10.1016/0041-0101(94)90111-2. [DOI] [PubMed] [Google Scholar]
  22. Lee S. H., Soyoola E., Chanmugam P., Hart S., Sun W., Zhong H., Liou S., Simmons D., Hwang D. Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. J Biol Chem. 1992 Dec 25;267(36):25934–25938. [PubMed] [Google Scholar]
  23. Masferrer J. L., Seibert K., Zweifel B., Needleman P. Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3917–3921. doi: 10.1073/pnas.89.9.3917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Osterrieder W. 9-Amino-1,2,3,4-tetrahydroacridine (THA) is a potent blocker of cardiac potassium channels. Br J Pharmacol. 1987 Nov;92(3):521–525. doi: 10.1111/j.1476-5381.1987.tb11352.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Parente L., Di Rosea M., Flower R. J., Ghiara P., Meli R., Persico P., Salmon J. A., Wood J. N. Relationship between the anti-phospholipase and anti-inflammatory effects of glucocorticoid-induced proteins. Eur J Pharmacol. 1984 Mar 23;99(2-3):233–239. doi: 10.1016/0014-2999(84)90246-2. [DOI] [PubMed] [Google Scholar]
  26. Payne A. N., de Nucci G. Anaphylaxis in guinea pigs induced by ovalbumin aerosol in vivo and in vitro methods. J Pharmacol Methods. 1987 Mar;17(1):83–90. doi: 10.1016/0160-5402(87)90040-4. [DOI] [PubMed] [Google Scholar]
  27. Pruzanski W., Vadas P., Browning J. Secretory non-pancreatic group II phospholipase A2: role in physiologic and inflammatory processes. J Lipid Mediat. 1993 Nov;8(3):161–167. [PubMed] [Google Scholar]
  28. Pruzanski W., Vadas P., Stefanski E., Urowitz M. B. Phospholipase A2 activity in sera and synovial fluids in rheumatoid arthritis and osteoarthritis. Its possible role as a proinflammatory enzyme. J Rheumatol. 1985 Apr;12(2):211–216. [PubMed] [Google Scholar]
  29. Pruzanski W., Wilmore D. W., Suffredini A., Martich G. D., Hoffman A. G., Browning J. L., Stefanski E., Sternby B., Vadas P. Hyperphospholipasemia A2 in human volunteers challenged with intravenous endotoxin. Inflammation. 1992 Oct;16(5):561–570. doi: 10.1007/BF00918980. [DOI] [PubMed] [Google Scholar]
  30. Radomski M., Moncada S. An improved method for washing of human platelets with prostacyclin. Thromb Res. 1983 May 15;30(4):383–389. doi: 10.1016/0049-3848(83)90230-x. [DOI] [PubMed] [Google Scholar]
  31. Rübsamen K., Breithaupt H., Habermann E. Biochemistry and pharmacology of the crotoxin complex. I. Subfractionation and recombination of the crotoxin complex. Naunyn Schmiedebergs Arch Pharmakol. 1971;270(3):274–288. doi: 10.1007/BF00997027. [DOI] [PubMed] [Google Scholar]
  32. SPECTOR W. G., WILLOUGHBY D. A. The demonstration of the role of mediators in turpentine pleurisy in rats by experimental suppression of the inflammatory changes. J Pathol Bacteriol. 1959 Jan;77(1):1–17. [PubMed] [Google Scholar]
  33. Salmon J. A. A radioimmunoassay for 6-keto-prostaglandin F1alpha. Prostaglandins. 1978 Mar;15(3):383–397. doi: 10.1016/0090-6980(78)90122-3. [DOI] [PubMed] [Google Scholar]
  34. Smith J. B., Willis A. L. Aspirin selectively inhibits prostaglandin production in human platelets. Nat New Biol. 1971 Jun 23;231(25):235–237. doi: 10.1038/newbio231235a0. [DOI] [PubMed] [Google Scholar]
  35. Vadas P., Hay J. B. Involvement of circulating phospholipase A2 in the pathogenesis of the hemodynamic changes in endotoxin shock. Can J Physiol Pharmacol. 1983 Jun;61(6):561–566. doi: 10.1139/y83-086. [DOI] [PubMed] [Google Scholar]
  36. Vadas P., Pruzanski W. Role of secretory phospholipases A2 in the pathobiology of disease. Lab Invest. 1986 Oct;55(4):391–404. [PubMed] [Google Scholar]
  37. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
  38. Verheij H. M., Boffa M. C., Rothen C., Bryckaert M. C., Verger R., de Haas G. H. Correlation of enzymatic activity and anticoagulant properties of phospholipase A2. Eur J Biochem. 1980 Nov;112(1):25–32. doi: 10.1111/j.1432-1033.1980.tb04982.x. [DOI] [PubMed] [Google Scholar]

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