Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1983 Aug;79(4):863–868. doi: 10.1111/j.1476-5381.1983.tb10530.x

The source of thromboxane and prostaglandins in experimental inflammation.

G A Higgs, S Moncada, J A Salmon, K Seager
PMCID: PMC2044931  PMID: 6652359

Abstract

Although cyclo-oxygenase products have been detected at inflammatory sites the tissue of origin remains uncertain. Inflammatory exudates were collected from rats 4, 6, 8, 12 or 24 h after subcutaneous implantation of carrageenin-impregnated sponges. Concentrations of the cyclo-oxygenase products prostaglandin E2 (PGE2), 6-oxo-PGF1 alpha and thromboxane B2 (TXB2) in inflammatory exudates and serum (obtained from blood clotted at 37 degrees C) were measured by specific radioimmunoassays. TXB2 concentrations in exudates increased to about 100 ng ml-1 at 8 h but decreased to less than 20 ng ml-1 after 24 h. PGE2 concentrations increased from 4-12 h and remained between 80 and 120 ng ml-1 from 12-24 h. 6-oxo-PGF1 alpha had the same time course as that of PGE2 but concentrations were approximately one third of PGE2 values. TXB2 concentrations in serum from thrombocytopaenic rats were less than 5% of control values. Thrombocytopaenia did not affect TXB2, PGE2 or 6-oxo-PGF1 alpha concentrations or total leukocyte numbers in inflammatory exudates. Methotrexate-induced neutropaenia did not affect serum TXB2 concentrations but cyclo-oxygenase products (including TXB2) in 6 h inflammatory exudates were reduced by 60-95%. Colchicine (1.0 mg kg-1 s.c.) prevented leukocyte accumulation in sponge exudates and this was accompanied by a reduction in TXB2, PGE2 and 6-oxo-PGF1 alpha concentrations at 6 h. These results indicate that platelets are the source of TXB2 in clotting blood but do not contribute to cyclo-oxygenase activity in experimental inflammation. The results also suggest that migrating leukocytes are the major source of thromboxane and to a lesser degree prostaglandins in acute 6 h inflammatory exudates.

Full text

PDF
863

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bombardieri S., Cattani P., Ciabattoni G., Di Munno O., Pasero G., Patrono C., Pinca E., Pugliese F. The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and nonsteroidal anti-inflammatory drugs. Br J Pharmacol. 1981 Aug;73(4):893–901. doi: 10.1111/j.1476-5381.1981.tb08743.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brodie M. J., Hensby C. N., Parke A., Gordon D. Is prostacyclin in the major pro-inflammatory prostanoid in joint fluid? Life Sci. 1980 Aug 18;27(7):603–608. doi: 10.1016/0024-3205(80)90310-0. [DOI] [PubMed] [Google Scholar]
  3. Chang W. C., Murota S., Matsuo M., Tsurufuji S. A new prostaglandin transformed from arachidonic acid in carrageenin-induced granuloma. Biochem Biophys Res Commun. 1976 Oct 18;72(4):1259–1264. doi: 10.1016/s0006-291x(76)80150-7. [DOI] [PubMed] [Google Scholar]
  4. Chang W. C., Murota S., Tsurufuji S. Thromboxane B2 transformed from arachidonic acid in carrageenin-induced granuloma. Prostaglandins. 1977 Jan;13(1):17–24. doi: 10.1016/0090-6980(77)90038-7. [DOI] [PubMed] [Google Scholar]
  5. Hamberg M., Svensson J., Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994–2998. doi: 10.1073/pnas.72.8.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Higgs G. A., Bunting S., Moncada S., Vane J. R. Polymorphonuclear leukocytes produce thromboxane A2-like activity during phagocytosis. Prostaglandins. 1976 Nov;12(5):749–757. doi: 10.1016/0090-6980(76)90050-2. [DOI] [PubMed] [Google Scholar]
  7. Higgs G. A., Harvey E. A., Ferreira S. H., Vane J. R. The effects of antiinflammatory drugs on the production of prostaglandins in vivo. Adv Prostaglandin Thromboxane Res. 1976;1:105–110. [PubMed] [Google Scholar]
  8. Higgs G. A., McCall E., Youlten L. J. A chemotactic role for prostaglandins released from polymorphonuclear leucocytes during phagocytosis. Br J Pharmacol. 1975 Apr;53(4):539–546. doi: 10.1111/j.1476-5381.1975.tb07392.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Humes J. L., Bonney R. J., Pelus L., Dahlgren M. E., Sadowski S. J., Kuehl F. A., Jr, Davies P. Macrophages synthesis and release prostaglandins in response to inflammatory stimuli. Nature. 1977 Sep 8;269(5624):149–151. doi: 10.1038/269149a0. [DOI] [PubMed] [Google Scholar]
  10. Moncada S., Gryglewski R., Bunting S., Vane J. R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976 Oct 21;263(5579):663–665. doi: 10.1038/263663a0. [DOI] [PubMed] [Google Scholar]
  11. Patrono C., Ciabattoni G., Pinca E., Pugliese F., Castrucci G., De Salvo A., Satta M. A., Peskar B. A. Low dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res. 1980 Feb 1;17(3-4):317–327. doi: 10.1016/0049-3848(80)90066-3. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Salmon J. A., Higgs G. A., Vane J. R., Bitensky L., Chayen J., Henderson B., Cashman B. Synthesis of arachidonate cyclo-oxygenase products by rheumatoid and nonrheumatoid synovial lining in nonproliferative organ culture. Ann Rheum Dis. 1983 Feb;42(1):36–39. doi: 10.1136/ard.42.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Samuelsson B., Goldyne M., Granström E., Hamberg M., Hammarström S., Malmsten C. Prostaglandins and thromboxanes. Annu Rev Biochem. 1978;47:997–1029. doi: 10.1146/annurev.bi.47.070178.005025. [DOI] [PubMed] [Google Scholar]
  15. Ubatuba F. B., Ferreira S. H. Platelets, Arthus-type reactions and inflammatory mediators. Agents Actions. 1976 Jul;6(4):483–489. doi: 10.1007/BF01973264. [DOI] [PubMed] [Google Scholar]
  16. Ubatuba F. B., Harvey E. A., Ferreira S. H. Are platelets important in inflammation? Agents Actions. 1975 Feb;5(1):31–34. doi: 10.1007/BF02027155. [DOI] [PubMed] [Google Scholar]
  17. Vargas J. R., Radomski M., Moncada S. The use of prostacyclin in the separation from plasma and washing of human platelets. Prostaglandins. 1982 Jun;23(6):929–945. doi: 10.1016/0090-6980(82)90135-6. [DOI] [PubMed] [Google Scholar]
  18. Willoughby D. A., Spector W. G. Inflammation in agranulocytotic rats. Nature. 1968 Sep 21;219(5160):1258–1258. doi: 10.1038/2191258a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES