Effect of acetylation on arthropathic activity of group A streptococcal peptidoglycan-polysaccharide fragments.
Purified group A streptococcal peptidoglycan-polysaccharide (PG-PS) fragments were either de-O-acylated, or acetylated and then de-O-acylated to yield N-acetylated PG-PS. Native PG-PS was poorly degraded, N-acetylated PG-PS was extensively degraded, and de-O-acylated PG-PS was only slightly degraded by hen egg white lysozyme. N-acetylated PG-PS was also extensively degraded by human lysozyme and partially degraded by rat serum or rat liver extract. After a single intraperitoneal injection of rats with a sterile, aqueous suspension, all PG-PS preparations induced acute arthritis. The acute arthritis induced by N-acetylated PG-PS was significantly more severe than that induced by native PG-PS; that induced by de-O-acylated PG-PS was of intermediate severity. After the acute reaction, rats injected with native PG-PS developed chronic relapsing erosive synovitis which remained severe for the duration of the experiment (83 days). In contrast, joint inflammation induced by N-acetylated PG-PS resolved within 6 weeks with little evidence of recurrent disease. Chronic arthritis induced by de-O-acylated PG-PS was of intermediate severity. In another assay of arthropathic activity, the arthritis in all rat ankle joints, which had been injected directly with native PG-PS, could be reactivated 3 weeks later by the intravenous injection of a small dose of PG. In contrast, only 50% of the joints initially injected with de-O-acylated PG-PS and none of the joints injected with N-acetylated PG-PS could be reactivated. These studies support the concepts that the resistance of PG-PS to muralytic digestion is crucial for chronic arthropathic activity and that the nature and degree of PG acetylation are important molecular determinants of the phlogistic activities of PG-PS polymers.
D000107:Acetylation; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D001168:Arthritis / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology*; D005260:Female; D009113:Muramidase / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology* / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D013297:Streptococcus pyogenes / Q000276:immunology*; D013329:Structure-Activity Relationship
D000942:Antigens, Bacterial; D010457:Peptidoglycan; D011135:Polysaccharides, Bacterial; D009113:Muramidase