Uric Acid pp 365-377 | Cite as

Role of the Leukocyte and Chemical Mediators of the Acute Gouty Attack

  • I. Spilberg
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 51)

Abstract

Experimental work in vivo (McCarty, 1970) has shown that the introduction of monosodium urate crystals into a joint cavity initiates an acute inflammatory response. Polymorphonuclear leukocytes are normally present in synovial fluid and phagocytosis of crystals by polymorphonuclear leukocytes occurs readily. Experimental work on animals has shown that the phagocytosis of crystals by polymorphonuclear leukocytes occurs independently of complement (Spilberg and Osterland, 1970). The crystals are taken into phagosomes which then merge with primary lysosomes to form phagolysosomes or secondary lysosomes. Electron microscopic studies indicate that after a crystal lies in contact with the membrane of the phagolysosome, dissolution of the membrane occurs and is followed by cell death (Schumacher and Phelps, 1968). Cell death, however, appears to be a slow process, since neutrophils which have previously ingested urate crystals in vitro have been reported to exhibit a normal phagocytic capacity for yeast (Turner et al., 1973). Weissmann and Rita (1972) have postulated that lysis of the lysosomal membrane is due to the interaction of weakly anionic urate crystals with the membrane, forming cooperative hydrogen bonds with phosphate esters of membrane phospholipids. Not only do urate crystals disrupt lysosomal membranes, they also lyse red cells (Wallingford and McCarty, 1971), the plasma membrane of polymorphonuclear leukocytes (Spilberg et al., 1975), and liposomes (Weissman and Rita, 1972), lamellar arrays of phospholipids containing cholesterol in their membranes.

Keywords

Cholesterol Aspirin Adenosine Histamine Turkey 

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