title: Bone-resorbing activity is expressed by rat macrophages in response to arthropathic streptococcal cell wall polymers.
abstract: Rat peritoneal macrophages stimulated in vivo by group A streptococcal peptidoglycan-polysaccharide (PG-APS) resorb bone as measured by solubilization of 45Ca from radiolabeled, devitalized bone chips. Activity was strain-dependent and correlated with the susceptibility of rat strains to PG-APS-induced arthritis. PG-APS-stimulated macrophages from the resistant Buf rat strain were not induced to resorb bone, but ingested equivalent concentrations of PG-APS compared to bone-resorbing macrophages from the arthritis-susceptible Lew strain. Resorptive activity peaked at three to five days and decreased to background levels by 10 days after injection. PG-APS-stimulated macrophages from congenitally athymic Lew rats were as effective as macrophages from heterozygous littermates at resorbing bone. Lew macrophages were also responsive to small, nonarthropathic PG-APS polymers generated by mutanolysin digestion. Resident peritoneal macrophages did not respond to stimulation by PG-APS in vitro. Indomethacin at a concentration of 10 micrograms/ml was an effective blockade against PG-APS-induced macrophage bone resorption in vitro, but catalase was ineffective. These results indicate that expression of rat macrophage bone-resorbing activity reflects genetic regulation of the response to PG-APS rather than a defect in ingestion of these polymers and imply that PG-APS-stimulated, bone-resorbing macrophages may contribute to early, initial bone destruction that occurs in inflammatory arthritis.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599.
authors.forename: L A
authors.initials: LA
authors.lastname: Bristol-Rothstein
authors.forename: J H
authors.initials: JH
authors.lastname: Schwab
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000276:immunology*; D002473:Cell Wall / Q000737:chemistry; D010450:Endopeptidases; D005260:Female; D007592:Joint Diseases / Q000139:chemically induced*; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D013045:Species Specificity; D013297:Streptococcus pyogenes; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D011135:Polysaccharides, Bacterial; C044260:streptococcal group A cell wall carbohydrate; D011451:Prostaglandin-Endoperoxide Synthases; D010450:Endopeptidases; C021816:mutanolysin