RESUMO
Proteinases are thought to be responsible for cartilage and bone erosion noted in chronic inflammatory conditions. Suramin [8-(3-benzamindo-4-meta-1-benzamindo)naphthalene-1,3,5-trisulfonic acid], 10(-5) and 10(-4) M, inhibited the release of a mouse macrophage-derived cartilage proteoglycan-degrading enzyme. At 10(-5) M it antagonized the activity of beta-glucuronidase and cathepsin D derived from the mouse macrophage, as well as similar enzymes secreted by rat macrophages in vivo. When cultured at 10(-4) M with rabbit knee cartilage, it antagonized the autolytic release of proteoglycan, indicating an inhibitory activity against a chondrocyte-derived neutral proteinase. After in vivo treatment at 10 mg/kg/day s.c., it was ineffective in preventing the cartilage and bone erosion noted in the adjuvant arthritic rat.
Assuntos
Cartilagem Articular/metabolismo , Suramina/farmacologia , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Ácido Aspártico Endopeptidases , Reabsorção Óssea/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Depressão Química , Endopeptidases/metabolismo , Feminino , Ativação de Macrófagos , Macrófagos/enzimologia , Masculino , Camundongos , Proteoglicanas/metabolismo , Coelhos , Ratos , Ratos EndogâmicosRESUMO
Mononuclear cell accumulation is of major importance in maintaining chronic inflammatory conditions. In an effort to model this phenomenon, 0.3 ml of a 1% carrageenan solution was injected into the pleural cavity of rats; at various times thereafter peripheral blood and pleural exudate samples were collected. Seventy-two hours after carrageenan injection, 82.3 +/- 3.7 x 10(6) cells (N = 6; mean +/- S.E.) were present in the pleural cavity; over 80% of these cells were macrophages as determined by morphologic and histochemical criteria. Animals treated with dexamethasone had a significantly reduced number of pleural macrophages. Animals treated with the nonsteroidal anti-inflammatory agents, naproxen and indomethacin, had an elevated intrapleural macrophage content. The number of intrapleural cells was not affected by the antirheumatic agents levamisole, d- and dl-penicillamine or gold sodium thiomalate. Animals treated with tilorone, dapsone, hydroxychloroquine, phenylmethane-sulfonyl fluoride and 1,10 phenanthroline had a reduced pleural cell count.