BONE-RESORBING ACTIVITY IS EXPRESSED BY RAT MACROPHAGES IN RESPONSE TO ARTHROPATHIC STREPTOCOCCAL CELL-WALL POLYMERS

Rat peritoneal macrophages stimulated in vivo by group A streptococcal peptidoglycan-polysaccharide (PG-APS) resorb bone as measured by solubilization of Ca-45 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 mug/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.