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Treatment of experimental erosive arthritis in rats by injection of the muralytic enzyme mutanolysin.

Abstract
A single intravenous injection into rats of 0.4 mg of the muralytic enzyme mutanolysin, given as long as 3 d after an arthropathic dose of peptidoglycan-polysaccharide polymers derived from group A streptococci (PG-APS), resulted in a complete resolution of acute arthritis and the prevention of chronic joint disease. When administration of mutanolysin was delayed until 14 d after the injection of PG-APS, a great reduction in the severity of chronic inflammation was still observed. Quantitation of the amount of PG-APS present in the limbs, spleen, and liver by a solid phase enzyme-linked immunoassay indicated that the tissues of mutanolysin-treated rats contained as much PG-APS as tissues of PBS-treated control rats. In addition, rats treated with mutanolysin immediately after receiving an intraperitoneal injection of PG-APS developed a transient limb edema similar to that seen in rats after the injection of PG-APS digested to a small fragment size in vitro with mutanolysin. We hypothesize that mutanolysin acts in vivo by degrading PG-APS to small fragments that persist but are no longer arthropathic.
AuthorsM J Janusz, C Chetty, R A Eisenberg, W J Cromartie, J H Schwab
JournalThe Journal of experimental medicine (J Exp Med) Vol. 160 Issue 5 Pg. 1360-74 (Nov 01 1984) ISSN: 0022-1007 [Print] United States
PMID6387033 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Peptidoglycan
  • Acetylmuramyl-Alanyl-Isoglutamine
  • peptidoglycan pentapeptide-mDap3
  • Muramidase
  • Endopeptidases
  • mutanolysin
Topics
  • Acetylmuramyl-Alanyl-Isoglutamine (analogs & derivatives)
  • Animals
  • Arthritis (drug therapy, etiology, pathology)
  • Cell Wall (enzymology)
  • Chronic Disease
  • Endopeptidases (administration & dosage, therapeutic use)
  • Female
  • Injections, Intravenous
  • Liver (pathology)
  • Lymph Nodes (pathology)
  • Muramidase (metabolism)
  • Peptidoglycan
  • Rats
  • Rats, Inbred Lew
  • Spleen (pathology)
  • Streptococcus pyogenes (enzymology)
  • Tarsal Joints (pathology)

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