Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Jul;78(1):108–114. doi: 10.1172/JCI112538

Release of leukotriene C4 by isolated, perfused rat small intestine in response to platelet-activating factor.

W Hsueh, F Gonzalez-Crussi, J L Arroyave
PMCID: PMC329538  PMID: 3459734

Abstract

We reported a rat model of necrotizing enterocolitis by injecting platelet-activating factor (PAF) into the mesenteric vascular bed, and suggested that leukotrienes (LT) are secondary mediators. The present study, using isolated, buffer-perfused rat small intestine, shows: Isolated, perfused small intestine synthesizes LTs in response to PAF. Leukotriene C4 (LTC4) was the predominant LT released. The initial vasoconstriction after PAF injection was due to a transient release of LTC4 since FPL 55712 pretreatment abolished the vasoconstriction. The sustained rise in perfusion pressure was also blocked by FPL 55712, which suggests that other vasoconstrictors released are regulated by LTs. The vasoconstrictor(s) responsible for sustained rise in perfusion pressure is unknown, but is not thromboxane. Most of the LT was released from intestinal tissue rather than mesenteric arteries. Vasodilating prostaglandins (PGs) were also released, probably secondary to LTs. The complex interaction of these lipid mediators (PAF, LTs, and PGs) and their subtle balance may affect the course of the disease.

Full text

PDF
111

Selected References

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

  1. Augstein J., Farmer J. B., Lee T. B., Sheard P., Tattersall M. L. Selective inhibitor of slow reacting substance of anaphylaxis. Nat New Biol. 1973 Oct 17;245(146):215–217. doi: 10.1038/newbio245215a0. [DOI] [PubMed] [Google Scholar]
  2. Bonnet J., Thibaudeau D., Bessin P. Dependency of the Paf-acether induced bronchospasm on the lipoxygenase pathway in the guinea-pig. Prostaglandins. 1983 Sep;26(3):457–466. doi: 10.1016/0090-6980(83)90180-6. [DOI] [PubMed] [Google Scholar]
  3. Camussi G., Aglietta M., Coda R., Bussolino F., Piacibello W., Tetta C. Release of platelet-activating factor (PAF) and histamine. II. The cellular origin of human PAF: monocytes, polymorphonuclear neutrophils and basophils. Immunology. 1981 Feb;42(2):191–199. [PMC free article] [PubMed] [Google Scholar]
  4. Camussi G., Aglietta M., Malavasi F., Tetta C., Piacibello W., Sanavio F., Bussolino F. The release of platelet-activating factor from human endothelial cells in culture. J Immunol. 1983 Nov;131(5):2397–2403. [PubMed] [Google Scholar]
  5. Dahlén S. E., Hansson G., Hedqvist P., Björck T., Granström E., Dahlén B. Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1712–1716. doi: 10.1073/pnas.80.6.1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dembinska-Kieć A., Simmet T., Peskar B. A. Release and vasoconstrictor effect of leukotriene C-like immunoreactive material in the anaphylactic guinea-pig mesenteric vascular bed. Eur J Pharmacol. 1984 Jun 1;101(3-4):259–262. doi: 10.1016/0014-2999(84)90166-3. [DOI] [PubMed] [Google Scholar]
  7. Ferreira S. H., Vane J. R. Prostaglandins: their disappearance from and release into the circulation. Nature. 1967 Dec 2;216(5118):868–873. doi: 10.1038/216868a0. [DOI] [PubMed] [Google Scholar]
  8. Garcia-Szabo R., Kern D. F., Malik A. B. Pulmonary vascular response to thrombin: effects of thromboxane synthetase inhibition with OKY-046 and OKY-1581. Prostaglandins. 1984 Dec;28(6):851–866. doi: 10.1016/0090-6980(84)90039-x. [DOI] [PubMed] [Google Scholar]
  9. Gonzalez-Crussi F., Hsueh W. Experimental model of ischemic bowel necrosis. The role of platelet-activating factor and endotoxin. Am J Pathol. 1983 Jul;112(1):127–135. [PMC free article] [PubMed] [Google Scholar]
  10. Hsueh W., Gonzalez-Crussi F., Arroyave J. L. Platelet-activating factor-induced ischemic bowel necrosis. An investigation of secondary mediators in its pathogenesis. Am J Pathol. 1986 Feb;122(2):231–239. [PMC free article] [PubMed] [Google Scholar]
  11. Hsueh W., Sun F. F., Henderson S. The biosynthesis of leukotriene B4, the predominant lipoxygenase product in rabbit alveolar macrophages, is enhanced during immune activation. Biochim Biophys Acta. 1985 Jun 14;835(1):92–97. [PubMed] [Google Scholar]
  12. LeDuc L. E., Needleman P. Regional localization of prostacyclin and thromboxane synthesis in dog stomach and intestinal tract. J Pharmacol Exp Ther. 1979 Oct;211(1):181–188. [PubMed] [Google Scholar]
  13. Lewis R. A., Austen K. F., Drazen J. M., Clark D. A., Marfat A., Corey E. J. Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3710–3714. doi: 10.1073/pnas.77.6.3710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. MacGlashan D. W., Jr, Schleimer R. P., Peters S. P., Schulman E. S., Adams G. K., 3rd, Newball H. H., Lichtenstein L. M. Generation of leukotrienes by purified human lung mast cells. J Clin Invest. 1982 Oct;70(4):747–751. doi: 10.1172/JCI110670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mencia-Huerta J. M., Benveniste J. Platelet-activating factor (PAF-acether) and macrophages. II. Phagocytosis-associated release of PAF-acether from rat peritoneal macrophages. Cell Immunol. 1981 Jan 15;57(2):281–292. doi: 10.1016/0008-8749(81)90087-3. [DOI] [PubMed] [Google Scholar]
  16. Omini C., Folco G. C., Viganò T., Rossoni G., Brunelli G., Berti F. Leukotriene-C4 induces generation of PGI2 and TXA2 in guinea-pig in vivo. Pharmacol Res Commun. 1981 Jul;13(7):633–640. doi: 10.1016/s0031-6989(81)80051-3. [DOI] [PubMed] [Google Scholar]
  17. Peskar B. M., Günter B., Peskar B. A. Prostaglandins and prostaglandin metabolites in human gastric juice. Prostaglandins. 1980 Aug;20(2):419–427. doi: 10.1016/s0090-6980(80)80059-1. [DOI] [PubMed] [Google Scholar]
  18. Peskar B. M., Weiler H., Kröner E. E., Peskar B. A. Release of prostaglandins by small intestinal tissue of man and rat in vitro and the effect of endotoxin in the rat in vivo. Prostaglandins. 1981;21 (Suppl):9–14. doi: 10.1016/0090-6980(81)90111-8. [DOI] [PubMed] [Google Scholar]
  19. Pinckard R. N., McManus L. M., Halonen M., Hanahan D. J. Acetyl glyceryl ether phosphorylcholine: platelet-activating factor. Int Arch Allergy Appl Immunol. 1981;66 (Suppl 1):127–136. doi: 10.1159/000232884. [DOI] [PubMed] [Google Scholar]
  20. Piper P. J., Samhoun M. N. The mechanism of action of leukotrienes C4 and D4 in guinea-pig isolated perfused lung and parenchymal strips of guinea pig, rabbit and rat. Prostaglandins. 1981 May;21(5):793–803. doi: 10.1016/0090-6980(81)90236-7. [DOI] [PubMed] [Google Scholar]
  21. Piper P. J., Vane J. R. Release of additional factors in anaphylaxis and its antagonism by anti-inflammatory drugs. Nature. 1969 Jul 5;223(5201):29–35. doi: 10.1038/223029a0. [DOI] [PubMed] [Google Scholar]
  22. Pologe L. G., Cramer E. B., Pawlowski N. A., Abraham E., Cohn Z. A., Scott W. A. Stimulation of human endothelial cell prostacyclin synthesis by select leukotrienes. J Exp Med. 1984 Oct 1;160(4):1043–1053. doi: 10.1084/jem.160.4.1043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Razin E., Mencia-Huerta J. M., Lewis R. A., Corey E. J., Austen K. F. Generation of leukotriene C4 from a subclass of mast cells differentiated in vitro from mouse bone marrow. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4665–4667. doi: 10.1073/pnas.79.15.4665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rouzer C. A., Scott W. A., Cohn Z. A., Blackburn P., Manning J. M. Mouse peritoneal macrophages release leukotriene C in response to a phagocytic stimulus. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4928–4932. doi: 10.1073/pnas.77.8.4928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Smith G. S., Warhurst G., Turnberg L. A. Synthesis and degradation of prostaglandin E2 in the epithelial and sub-epithelial layers of the rat intestine. Biochim Biophys Acta. 1982 Dec 13;713(3):684–687. doi: 10.1016/0005-2760(82)90331-9. [DOI] [PubMed] [Google Scholar]
  26. Vane J. R. The release and fate of vaso-active hormones in the circulation. Br J Pharmacol. 1969 Feb;35(2):209–242. doi: 10.1111/j.1476-5381.1969.tb07982.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vargaftig B. B., Chignard M., Benveniste J., Lefort J., Wal F. Background and present status of research on platelet-activating factor (PAF-acether). Ann N Y Acad Sci. 1981;370:119–137. doi: 10.1111/j.1749-6632.1981.tb29727.x. [DOI] [PubMed] [Google Scholar]
  28. Walker R., Wilson K. A. Gastroenterology, prostaglandins, bradykinin, and rat ileum. Adv Prostaglandin Thromboxane Res. 1980;8:1573–1575. [PubMed] [Google Scholar]
  29. Weller P. F., Lee C. W., Foster D. W., Corey E. J., Austen K. F., Lewis R. A. Generation and metabolism of 5-lipoxygenase pathway leukotrienes by human eosinophils: predominant production of leukotriene C4. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7626–7630. doi: 10.1073/pnas.80.24.7626. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES