UPTAKE OF TOXIC SILICA PARTICLES BY ISOLATED RAT-LIVER MACROPHAGES (KUPFFER CELLS) IS RECEPTOR MEDIATED AND CAN BE BLOCKED BY COMPETITION

Silica particles (quartz dust) are toxic to macrophages after their uptake into these cells. These experiments describe the opsonization mechanism(s) and macrophage receptor(s) involved in silica uptake. Freshly isolated rat liver macrophages (Kupffer cells) were incubated at 37-degrees-C with silica particles in the presence or absence of autologous or heterologous plasma or purified plasma fibronectin and cell viability was assessed at various times. Within 60 min of coincubation, > 80% of macrophages were lysed in the presence of plasma or purified fibronectin but not in their absence (viability > 90%). Lysis was slower with defibronectinized plasma (28% in 60 min). Macrophages could be protected from lysis by addition of the monosaccharide N-acetyl-D-galactosamine but not by N-acetyl-D-glucosamine. Galactosylated serum albumin but not mannosylated albumin or native albumin exerted full protection from lysis. The pentapeptide GRGDS also prevented macrophage lysis in synergy with N-acetyl-galactosamine. Enzymatic deglycosylation of fibronectin reduced lysis significantly. These findings indicate an important opsonizing activity for fibronectin and dual recognition via the lectin-like galactose-specific binding activity of membrane-associated C-reactive protein and by integrin receptor(s). Binding experiments (at 4-degrees-C) revealed initial binding as primarily galactose-inhibitable, suggesting integrin-mediated binding as a later event necessary for effective uptake.