Soluble peptidoglycan-polysaccharide fragments of the bacterial cell wall induce acute inflammation.
Peptidoglycan (PG)-polysaccharide (PS) polymers derived from group A streptococcal cell walls were solubilized by M-1 mutanolysin (endo-N-acetylmuramidase) and phage-associated lysin (N-acetylmuramyl-l-alanine amidase). Fragments were isolated by ultrafiltration and a series of gel filtrations and were injected intravenously into Sprague-Dawley rats. No fragments with a molecular weight of less than 5 x 10(6) were able to induce arthritis by systemic injection. However, the enzyme-derived fragments displayed a new biological activity. High-molecular-weight PG-PS fragments ( congruent with500,000) derived from mutanolysin digests induced a severe edematous reaction in the front and hind limbs. The response started 5 to 10 min postinjection, reached maximum intensity in approximately 30 min, and disappeared by 10 h. The smallest dose capable of eliciting the response was 0.31 mug/g of body weight. Low-molecular-weight PG-PS ( congruent with30,000) derived from the mutanolysin digests and the PG-PS fragments isolated from phage-associated lysin digests also induced edema; however, a higher dose was required to elicit the same response as that produced by high-molecular-weight PG-PS fragments. The active fragments contained rhamnose, glucosamine, muramic acid, alanine, glutamic acid, and lysine in various molar ratios. PG-PS fragments obtained by sonic degradation of cell walls (molecular weight >/=5.3 x 10(6)), as well as enzyme-treated PG preparations and muramyl dipeptide, failed to elicit the response. These findings indicate that PG-PS fragments of sizes too small to be arthritogenic can affect the vascular endothelium to induce a rapidly developing edema. Fragments with this biological property could have a key role in the pathogenesis of experimental arthritis by influencing the tissue distribution of arthritogenic PG-PS.
D000818:Animals; D004487:Edema / Q000139:chemically induced*; D010450:Endopeptidases; D008970:Molecular Weight; D010457:Peptidoglycan / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D011135:Polysaccharides, Bacterial / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013297:Streptococcus pyogenes / Q000032:analysis*
D010457:Peptidoglycan; D011135:Polysaccharides, Bacterial; D010450:Endopeptidases; C021816:mutanolysin