Treatment of experimental erosive arthritis in rats by injection of the muralytic enzyme mutanolysin.
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.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives; D000818:Animals; D001168:Arthritis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002473:Cell Wall / Q000201:enzymology; D002908:Chronic Disease; D010450:Endopeptidases / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007275:Injections, Intravenous; D008099:Liver / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D009113:Muramidase / Q000378:metabolism; D010457:Peptidoglycan; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000473:pathology; D013297:Streptococcus pyogenes / Q000201:enzymology; D013640:Tarsal Joints / Q000473:pathology
D010457:Peptidoglycan; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C032972:peptidoglycan pentapeptide-mDap3; D009113:Muramidase; D010450:Endopeptidases; C021816:mutanolysin