Skip to main content
NCBI home page
Gut logoLink to Gut
. 1996 Mar;38(3):355–361. doi: 10.1136/gut.38.3.355

Platelet activating factor: release from colonic mucosa in patients with ulcerative colitis and its effect on colonic secretion.

T D Wardle 1, L Hall 1, L A Turnberg 1
PMCID: PMC1383062  PMID: 8675086

Abstract

Inflammatory mediators have been implicated in the pathophysiology of ulcerative colitis. They may stimulate intestinal secretion and contribute to the production of diarrhoea. Platelet activating factor (PAF) may be responsible for a high proportion of this secretory response. Biopsy specimens from inflamed and quiescent mucosa of patients with ulcerative colitis and normal human colonic mucosa were cultured or co-cultured. The release of PAF, prostaglandin E2, and leukotriene D4 into the culture medium was measured and the ability of this culture medium, from inflamed and normal tissues, to influence secretion in rat colonic mucosa was assessed. PAF was liberated by inflamed tissue. Its release from quiescent but not normal tissue was stimulated by medium in which inflamed mucosal biopsy tissues had been cultured and by exogenous bradykinin and 5-hydroxytryptamine, but not by histamine. PAF stimulated eicosanoid production. The rise in short circuit current produced in vitro by inflamed tissue culture medium was inhibited by the PAF receptor antagonist (CV 6209) (46%) (32.4 (2.9) v 17.5 (1.19) muA.cm-2, p < 0.005) and further by combined cyclooxygenase and lipoxygenase inhibition (indomethacin plus ICI 207968) (58%) (32.4 (2.9) v 13.6 (1.9) muA.cm-2, p < 0.005). Mepacrine and hydrocortisone attenuated considerably the electrical response evoked by medium from inflamed mucosa to a similar extent (32.4 (2.9) v 6.3 (1.2) v 5.1 (0.9) muA.cm-2, p < 0.001). These data suggest that PAF accounted for 46% of the culture medium secretory effect. Thus, any attempt to block its release in patients with ulcerative colitis may have only a partial effect on their symptoms.

Full text

PDF
355

Selected References

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

  1. Albert D. H., Snyder F. Biosynthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) from 1-alkyl-2-acyl-sn-glycero-3-phosphocholine by rat alveolar macrophages. Phospholipase A2 and acetyltransferase activities during phagocytosis and ionophore stimulation. J Biol Chem. 1983 Jan 10;258(1):97–102. [PubMed] [Google Scholar]
  2. Benveniste J., Henson P. M., Cochrane C. G. Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor. J Exp Med. 1972 Dec 1;136(6):1356–1377. doi: 10.1084/jem.136.6.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bern M. J., Sturbaum C. W., Karayalcin S. S., Berschneider H. M., Wachsman J. T., Powell D. W. Immune system control of rat and rabbit colonic electrolyte transport. Role of prostaglandins and enteric nervous system. J Clin Invest. 1989 Jun;83(6):1810–1820. doi: 10.1172/JCI114086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chignard M., Le Couedic J. P., Tence M., Vargaftig B. B., Benveniste J. The role of platelet-activating factor in platelet aggregation. Nature. 1979 Jun 28;279(5716):799–800. doi: 10.1038/279799a0. [DOI] [PubMed] [Google Scholar]
  5. Doebber T. W., Wu M. S., Shen T. Y. Platelet activating factor intravenous infusion in rats stimulates vascular lysosomal hydrolase secretion independent of blood neutrophils. Biochem Biophys Res Commun. 1984 Dec 28;125(3):980–987. doi: 10.1016/0006-291x(84)91380-9. [DOI] [PubMed] [Google Scholar]
  6. Eliakim R., Karmeli F., Razin E., Rachmilewitz D. Role of platelet-activating factor in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine and prednisolone. Gastroenterology. 1988 Nov;95(5):1167–1172. doi: 10.1016/0016-5085(88)90346-0. [DOI] [PubMed] [Google Scholar]
  7. Hawkey C. J., Rampton D. S. Prostaglandins and the gastrointestinal mucosa: are they important in its function, disease, or treatment? Gastroenterology. 1985 Nov;89(5):1162–1188. doi: 10.1016/0016-5085(85)90225-2. [DOI] [PubMed] [Google Scholar]
  8. Hopkins N. K., Schaub R. G., Gorman R. R. Acetyl glyceryl ether phosphorylcholine (PAF-acether) and leukotriene B4-mediated neutrophil chemotaxis through an intact endothelial cell monolayer. Biochim Biophys Acta. 1984 Sep 14;805(1):30–36. doi: 10.1016/0167-4889(84)90033-8. [DOI] [PubMed] [Google Scholar]
  9. Humphrey D. M., McManus L. M., Satouchi K., Hanahan D. J., Pinckard R. N. Vasoactive properties of acetyl glyceryl ether phosphorylcholine and analogues. Lab Invest. 1982 Apr;46(4):422–427. [PubMed] [Google Scholar]
  10. Hwang S. B., Lam M. H., Pong S. S. Ionic and GTP regulation of binding of platelet-activating factor to receptors and platelet-activating factor-induced activation of GTPase in rabbit platelet membranes. J Biol Chem. 1986 Jan 15;261(2):532–537. [PubMed] [Google Scholar]
  11. Lapetina E. G. Platelet-activating factor stimulates the phosphatidylinositol cycle. Appearance of phosphatidic acid is associated with the release of serotonin in horse platelets. J Biol Chem. 1982 Jul 10;257(13):7314–7317. [PubMed] [Google Scholar]
  12. Lin A. H., Morton D. R., Gorman R. R. Acetyl glyceryl ether phosphorylcholine stimulates leukotriene B4 synthesis in human polymorphonuclear leukocytes. J Clin Invest. 1982 Nov;70(5):1058–1065. doi: 10.1172/JCI110693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McManus L. M., Hanahan D. J., Demopoulos C. A., Pinckard R. N. Pathobiology of the intravenous infusion of acetyl glyceryl ether phosphorylcholine (AGEPC), a synthetic platelet-activating factor (PAF), in the rabbit. J Immunol. 1980 Jun;124(6):2919–2924. [PubMed] [Google Scholar]
  14. O'Flaherty J. T., Thomas M. J., Hammett M. J., Carroll C., McCall C. E., Wykle R. L. 5-L-hydroxy-6,8,11,14-eicosatetraenoate potentiates the human neutrophil degranulating action of platelet-activating factor. Biochem Biophys Res Commun. 1983 Feb 28;111(1):1–7. doi: 10.1016/s0006-291x(83)80108-9. [DOI] [PubMed] [Google Scholar]
  15. Rampton D. S., Sladen G. E. Prostaglandin synthesis inhibitors in ulcerative colitis: flurbiprofen compared with conventional treatment. Prostaglandins. 1981 Mar;21(3):417–425. doi: 10.1016/0090-6980(81)90087-3. [DOI] [PubMed] [Google Scholar]
  16. Rampton D. S., Sladen G. E. Relapse of ulcerative proctocolitis during treatment with non-steroidal anti-inflammatory drugs. Postgrad Med J. 1981 May;57(667):297–299. doi: 10.1136/pgmj.57.667.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sánchez-Crespo M., Alonso F., Egido J. Platelet-activating factor in anaphylaxis and phagocytosis. I. Release from human peripheral polymorphonuclears and monocytes during the stimulation by ionophore A23187 and phagocytosis but not from degranulating basophils. Immunology. 1980 Aug;40(4):645–655. [PMC free article] [PubMed] [Google Scholar]
  18. USSING H. H., ZERAHN K. Active transport of sodium as the source of electric current in the short-circuited isolated frog skin. Acta Physiol Scand. 1951 Aug 25;23(2-3):110–127. doi: 10.1111/j.1748-1716.1951.tb00800.x. [DOI] [PubMed] [Google Scholar]
  19. Valone F. H., Goetzl E. J. Specific binding by human polymorphonuclear leucocytes of the immunological mediator 1-O-hexadecyl/octadecyl-2-acetyl-sn-glycero-3-phosphorylcholine. Immunology. 1983 Jan;48(1):141–149. [PMC free article] [PubMed] [Google Scholar]
  20. Wardle T. D., Hall L., Turnberg L. A. Inter-relationships between inflammatory mediators released from colonic mucosa in ulcerative colitis and their effects on colonic secretion. Gut. 1993 Apr;34(4):503–508. doi: 10.1136/gut.34.4.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wardle T. D., Hall L., Turnberg L. A. Use of coculture of colonic mucosal biopsies to investigate the release of eicosanoids by inflamed and uninflamed mucosa from patients with inflammatory bowel disease. Gut. 1992 Dec;33(12):1644–1651. doi: 10.1136/gut.33.12.1644. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES