Synthesis of arachidonate oxidation products by synovial joint tissues during the development of chronic erosive arthritis.
An animal model, antigen-induced arthritis in the rabbit, was used to investigate the synthesis of arachidonic acid oxidation products (eicosanoids) by tissues of the knee joints during the initiation and early phase of this developing chronic destructive lesion. High concentrations of immunoreactive prostaglandin E2 and immunoreactive leukotriene B4 were found to be present in the synovial fluid in the early lesion. These levels rapidly declined, as did the ability of the infiltrating cells of the arthritic joint fluids to synthesize leukotriene B4. Articular cartilage and synovial lining were maintained for 24 hours in nonproliferative organ culture, and the synthesis of eicosanoids was measured by assay of the culture fluids. The synovial lining was the major source of eicosanoids. Synthesis of prostaglandin E2, prostacyclin, thromboxane A2, and leukotriene B4 by the arthritic synovial lining was low during the first few days, but reached maximal values between day 5 and day 15 of disease duration. Maximal eicosanoid production occurred around the time that damage to articular cartilage and bone has been reported to occur, though it is not certain that these two events are linked. It was demonstrated that, in chronic lesions, the arthritic synovial lining was still producing elevated levels of eicosanoids compared with levels in the control tissue.
Henderson
B
B
Department of Mediator Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, UK.
Higgs
G A
GA
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001168:Arthritis / Q000378:metabolism*; D001169:Arthritis, Experimental / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002358:Cartilage, Articular / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis; D007596:Joints / Q000378:metabolism*; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D008297:Male; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction; D011458:Prostaglandins E / Q000096:biosynthesis; D011817:Rabbits; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011458:Prostaglandins E; D007975:Leukotriene B4; D000001:Calcimycin; D013928:Thromboxane A2; D011464:Epoprostenol; D015232:Dinoprostone