Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Feb;82(4):1232–1236. doi: 10.1073/pnas.82.4.1232

Circulating hydroxy fatty acids in familial Mediterranean fever.

P S Aisen, K A Haines, W Given, S B Abramson, M Pras, C Serhan, M Hamberg, B Samuelsson, G Weissmann
PMCID: PMC397229  PMID: 3919389

Abstract

Episodes of fever, serositis, and arthritis in familial Mediterranean fever (FMF) suggested circulating mediators of acute inflammation (e.g., neutrophil activation). The mean serum neutrophil-aggregating activity of 51 FMF patients was 2.5 +/- 0.2 cm2/min, compared to 1.0 +/- 0.1 cm2/min in 20 normal controls (P less than 0.0002). Lipid extracts of FMF sera retained neutrophil-aggregating activity and had UV absorbance peaks at 269 and 279 nm, indicating the presence of lipids with a conjugated triene structure. Chromatography of extracts yielded peaks that were coeluted with reference dihydroxyicosatetraenoic acids, had UV absorbance peaks at 259, 269, and 279 nm, and possessed neutrophil-aggregating activity. The presence of leukotriene B4 was excluded by chromatography following methyl-esterification. Monohydroxy compounds identified in FMF extracts by gas chromatography/mass spectrometry included 5-hydroxyicosatetraenoic acid, and 9- and 13-hydroxyoctadecadienoic acids. Hydroxy acids were present in 19 of 31 FMF sera and absent in extracts of sera from 8 patients with active systemic lupus erythematosus, 7 with fever from infection, and 12 normal controls. The finding of circulating mono- and dihydroxy fatty acids in FMF suggests that defects in the formation or elimination of these compounds might play a role in the pathogenesis of FMF.

Full text

PDF
1232

Selected References

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

  1. Abramson S. B., Given W. P., Edelson H. S., Weissmann G. Neutrophil aggregation induced by sera from patients with active systemic lupus erythematosus. Arthritis Rheum. 1983 May;26(5):630–636. doi: 10.1002/art.1780260509. [DOI] [PubMed] [Google Scholar]
  2. BRICK I. B., CAJIGAS M. Benign paroxysmal peritonitis; surgical and histologic findings. N Engl J Med. 1951 May 24;244(21):786–790. doi: 10.1056/NEJM195105242442102. [DOI] [PubMed] [Google Scholar]
  3. Bar-Eli M., Ehrenfeld M., Levy M., Gallily R., Eliakim M. Leukocyte chemotaxis in recurrent polyserositis (familial Mediterranean fever). Am J Med Sci. 1981 Jan-Feb;281(1):15–18. doi: 10.1097/00000441-198101000-00002. [DOI] [PubMed] [Google Scholar]
  4. Bar-Eli M., Territo M. C., Peters R. S., Schwabe A. D. A neutrophil lysozyme leak in patients with familial Mediterranean fever. Am J Hematol. 1981 Dec;11(4):387–395. doi: 10.1002/ajh.2830110407. [DOI] [PubMed] [Google Scholar]
  5. Borgeat P., Hamberg M., Samuelsson B. Transformation of arachidonic acid and homo-gamma-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipoxygenases. J Biol Chem. 1976 Dec 25;251(24):7816–7820. [PubMed] [Google Scholar]
  6. Borgeat P., Samuelsson B. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci U S A. 1979 May;76(5):2148–2152. doi: 10.1073/pnas.76.5.2148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Borgeat P., Samuelsson B. Metabolism of arachidonic acid in polymorphonuclear leukocytes. Structural analysis of novel hydroxylated compounds. J Biol Chem. 1979 Aug 25;254(16):7865–7869. [PubMed] [Google Scholar]
  8. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  9. Craddock P. R., Hammerschmidt D., White J. G., Dalmosso A. P., Jacob H. S. Complement (C5-a)-induced granulocyte aggregation in vitro. A possible mechanism of complement-mediated leukostasis and leukopenia. J Clin Invest. 1977 Jul;60(1):260–264. doi: 10.1172/JCI108763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dinarello C. A., Chusid M. J., Fauci A. S., Gallin J. I., Dale D. C., Wolff S. M. Effect of prophylactic colchicine therapy on leukocyte function in patients with familial Mediterranean fever. Arthritis Rheum. 1976 May-Jun;19(3):618–622. doi: 10.1002/art.1780190315. [DOI] [PubMed] [Google Scholar]
  11. Dinarello C. A., Wolff S. M., Goldfinger S. E., Dale D. C., Alling D. W. Colchicine therapy for familial mediterranean fever. A double-blind trial. N Engl J Med. 1974 Oct 31;291(18):934–937. doi: 10.1056/NEJM197410312911804. [DOI] [PubMed] [Google Scholar]
  12. Gallin J. I., Rosenthal A. S. The regulatory role of divalent cations in human granulocyte chemotaxis. Evidence for an association between calcium exchanges and microtubule assembly. J Cell Biol. 1974 Sep;62(3):594–609. doi: 10.1083/jcb.62.3.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Given W. P., Edelson H. S., Kaplan H. B., Aisen P., Weissmann G., Abramson S. B. Generation of C5-derived peptides and other immune reactants in the sera of patients with systemic lupus erythematosus. Arthritis Rheum. 1984 Jun;27(6):631–637. doi: 10.1002/art.1780270605. [DOI] [PubMed] [Google Scholar]
  14. Goldstein I. M., Brai M., Osler A. G., Weissmann G. Lysosomal enzyme release from human leukocytes: mediation by the alternate pathway of complement activation. J Immunol. 1973 Jul;111(1):33–37. [PubMed] [Google Scholar]
  15. Hamberg M. Decomposition of unsaturated fatty acid hydroperoxides by hemoglobin: Structures of major products of 13L-hydroperoxy-9,11-octadecadienoic acid. Lipids. 1975 Feb;10(2):87–92. doi: 10.1007/BF02532161. [DOI] [PubMed] [Google Scholar]
  16. Hoffstein S., Goldstein I. M., Weissmann G. Role of microtubule assembly in lysosomal enzyme secretion from human polymorphonuclear leukocytes. A reevaluation. J Cell Biol. 1977 Apr;73(1):242–256. doi: 10.1083/jcb.73.1.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kaplan H. B., Edelson H. S., Friedman R., Weissmann G. The roles of degranulation and superoxide anion generation in neutrophil aggregation. Biochim Biophys Acta. 1982 Sep 13;721(1):55–63. doi: 10.1016/0167-4889(82)90023-4. [DOI] [PubMed] [Google Scholar]
  18. Matzner Y., Partridge R. E., Levy M., Babior B. M. Diminished activity of a chemotactic inhibitor in synovial fluids from patients with familial Mediterranean fever. Blood. 1984 Mar;63(3):629–633. [PubMed] [Google Scholar]
  19. Serhan C. N., Radin A., Smolen J. E., Korchak H., Samuelsson B., Weissmann G. Leukotriene B4 is a complete secretagogue in human neutrophils: a kinetic analysis. Biochem Biophys Res Commun. 1982 Aug;107(3):1006–1012. doi: 10.1016/0006-291x(82)90622-2. [DOI] [PubMed] [Google Scholar]
  20. Smith M. J., Ford-Hutchinson A. W., Bray M. A. Leukotriene B: a potential mediator of inflammation. J Pharm Pharmacol. 1980 Jul;32(7):517–518. doi: 10.1111/j.2042-7158.1980.tb12985.x. [DOI] [PubMed] [Google Scholar]
  21. Sohar E., Gafni J., Pras M., Heller H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med. 1967 Aug;43(2):227–253. doi: 10.1016/0002-9343(67)90167-2. [DOI] [PubMed] [Google Scholar]
  22. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  23. Territo M. C., Peters R. S., Cline M. J. Leukocyte function in familial Mediterranean fever. Am J Hematol. 1976;1(3):307–311. doi: 10.1002/ajh.2830010304. [DOI] [PubMed] [Google Scholar]
  24. Zemer D., Revach M., Pras M., Modan B., Schor S., Sohar E., Gafni J. A controlled trial of colchicine in preventing attacks of familial mediterranean fever. N Engl J Med. 1974 Oct 31;291(18):932–934. doi: 10.1056/NEJM197410312911803. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES