, Volume 12, Issue 6, pp 549–561 | Cite as

Edema-inducing activity of phospholipase A2 purified from human synovial fluid and inhibition by aristolochic acid

  • B. S. Vishwanath
  • A. A. Fawzy
  • R. C. Franson
Original Articles


A neutral-active, Ca2+-dependent phospholipase A2 (PLA2) purified 11,000-fold from human synovial fluid (HSF) induced edema when injected into the mouse foot pad. The edema produced by HSF-PLA2 was dose-dependent and was positively correlated with the dose-dependent in vitro expression of PLA2 activity. Maximum edema was achieved within 45 min after the injection and persisted for atleast 6 h. Aristolochic acid [8-methoxy-6-nitrophenanthro(3,4-d)-1,3-dioxole-5-carboxylic acid], a major chemical component derived from various species ofAristolochia plant, produced a dose-dependent inhibition of in vitro phospholipid hydrolysis by HSF-PLA2, porcine pancreatic PLA2, snake venom (Naja naja) PLA2, and PLA2 isolated from human platelet. The sensitivity of these PLA2s to inhibition by aristolochic acid varied markedly: HSF-PLA2>N.naja PLA2>human platelet PLA2>porcine pancreatic PLA2. The inhibition of HSF-PLA2 by aristolochic acid was independent of substrate concentration (18–144ΜM and Ca2+ concentration (0.1–4.0 mM). These observations indicate that inhibition of HSF-PLA2 by aristolochic acid may result from direct interaction with the enzyme. When aristolochic acid was mixed with HSF-PLA2 and then injected into the mouse foot pad, edema was inhibited in a dose-dependent manner and was positively correlated with in vitro inhibition of PLA2 activity. Alkylation of HSF-PLA2 withp-bromophenacyl bromide concomitantly inhibited both enzyme and edema-inducing activity. These results clearly demonstrate that the neutral-active, Ca2+-dependent PLA2 isolated from human synovial fluid is proinflammatory and that catalytic activity is positively correlated with in vivo proinflammatory effects.


Substrate Concentration Chemical Component Human Platelet Snake Venom Aristolochic Acid 
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Copyright information

© Plenum Publishing Corporation 1988

Authors and Affiliations

  • B. S. Vishwanath
    • 1
  • A. A. Fawzy
    • 1
  • R. C. Franson
    • 1
  1. 1.Department of Biochemistry and Molecular BiophysicsMedical College of Virginia, Virginia Commonwealth UniversityRichmond

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