Abstract
Platelet activating factor (PAF-acether) is a potent pro-inflammatory mediator. The possible involvement of this molecule in the pathogenesis of chronic erosive arthritis has been investigated using an animal model, antigen-induced arthritis in the rabbit, which closely resembles rheumatoid arthritis. The arthritic joint fluids from rabbits with antigen-induced arthritis contained low levels of PAF-acether in the acute stages of the disease. However, PAF-acether was not detectable in the chronic stages of the lesion. The biologically inactive precursor/metabolite of PAF-acether, lyso-PAF-acether, was detectable in both control and arthritic joint washes. However, the levels of lyso-PAF-acether in the arthritic joint fluids were significantly elevated above those of control in the acute stages of the disease, but not in the chronic stages. Intra-articular injection of PAF-acether at doses up to 100 times the levels detected in the acute stages of this model did not induce joint swelling or leucocyte accumulation in normal rabbits. This study suggests that PAF-acether may contribute to the acute phase of antigeninduced arthritis but is less likely to be involved in the chronic processes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
D. L. Gardner,The pathology of rheumatoid arthritis. Edward Arnold, London 1972.
E. Goetzl, C. K. Derian, A. I. Tauber and F. H. Valone,Novel effects of 1-o-hexadecyl-2-acyl-SN-glycero-3-phosphorylcholine mediators of human leukocyte function: delineation of the specific roles of the acyl substituents. Biochem. Biophys. Res. Comm.94, 881–888 (1980).
C. B. Archer, C. P. Page, J. Morley and D. M. MacDonald,Accumulation of inflammatory cells in response to intracutaneous platelet activating factor (PAF-acether) in man. Br. J. Dermatol.112, 285–290 (1985).
G. Virella, M. F. L. Lopes-Virella, C. Shuler, T. Sherwood, G. A. espinoza, P. Winocour and J. A. Colwell,Release of PAF by human polymorphonuclear leucocytes stimulated by immune complexes bound to sepharose particles and human eruthrocytes. Immunology50, 43–49 (1983).
J.-M. Mencia-Huerta and J. Benveniste,Platelet-activating factor (PAF-acether) and macrophages II. Phagocytosis-associated release of PAF-acether from rat peritoneal macrophages. Cell. Immunol.57, 281–292 (1981).
R. J. Winchester, H. G. Kunkel and V. J. Agnello,Occurrence of γ-globulin complexes in serum and joint fluid of rheumatoid arthritis patients: use of monoclonal rheumatoid factors as reagents for their demonstration. J. Exp. Med.134, 286s-295s (1971).
D. C. Dumonde and L. E. Glynn,The production of arthritis in rabbits by an immunological reaction to fibrin. Br. J. Exp. Path.43, 373–383 (1962).
D. H. Albert and F. Snyder,Biosynthesis of 1-alkyl-2-acetyl-SN-glycero-phosphocholine (platelet-activating factor) from 1-alkyl-2-acyl-SN-glycero-3-phosphocholine by rat alveolar macrophages. Phospholipase A 2 and acetyl transferase activities during phagocytosis and ionophore stimulation. J. Biol. Chem.258, 97–102 (1983).
M. L. Blank, T.-C. Lee, V. Fitzgerald and F. Snyder,A specific acetyl hydrolase for 1-alkyl-2-acetyl-SN-glycero-3-phosphocholine (a hypotensive and platelet activating lipid). J. Biol. Chem.256, 175–178 (1981).
L. Parente and R. J. Flower,Hydrocortisone and macrocortin inhibit the zymosan-induced release of lyso-PAF from rat peritoneal leucocytes. Life Sci.36, 1225–1231 (1985).
B. B. Vargaftig, M. Chignard, J. Benveniste, J. Lefort and F. Wal,Background and present status of research on platelet- activating factor (PAF-acether). Ann. N.Y. Acad. Sci.370, 119–137 (1981).
G. A. Higgs, J. A. Salmon and J. A. Spayne,The inflammatory effects of hydroperoxy and hydroxy acid products of arachidonate lipoxygenase in rabbit skin. Br. J. Pharmacol.74, 429–433 (1981).
R. P. Carlson, J. Chang and A. J. Lewis,Does leukotriene B 4 play a role in urate-induced synovitis in dogs? Br. J. Pharmacol.86, 521P (1985).
E. R. Pettipher, G. A. Higgs and B. Henderson,Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc. Natl. Acad. Sci.83, 8749–8753 (1986).
P. G. Braquet,Treatment and prevention of PAF-acether-induced sickness by a new series of highly specific inhibitors. G. B. Patent,8, 418–424 (1984).
T. Y. Shen, S.-B. Hwang, M. Chang, T. W. Doebber, M.-H. Lam, M. S. Wu, X. Wang, G. Q. Han and R. E. Li,Characterisation of platelet activating factor receptor antagonist isolated from haifentens (Piper, futokadsura): specific inhibition of in vitro and in vivo platelet activating factor-induced effects. Proc. Natl. Acad. Sci. USA82, 672–676 (1985).
Z. Terashita, S. Tsushima, Y. Yoshioka, H. Nomura, Y. Inada and K. Nishikawa,CV-3988; A specific antagonist of platelet activating factor (PAF). Life Sci32, 1975–1982 (1983).
P. G. Hellewell and T. J. Williams,A specific antagonist of platelet-activating factor suppresses oedema formation in an Arthus reaction but not oedema induced by leukocyte chemoattractants in rabbit skin. J. Immunol.137, 302–307 (1986).
A. C. Issekutz and M. Szpejda,Evidence that platelet activating factor may mediate some acute inflammatory responses. Studies with the platelet activating factor antagonist, CV-3988. Lab. Invest.54, 275–281 (1986).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pettipher, E.R., Higgs, G.A. & Henderson, B. PAF-acether in chronic arthritis. Agents and Actions 21, 98–103 (1987). https://doi.org/10.1007/BF01974929
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01974929