Actin-induced reticuloendothelial phagocytic depression as mediated by its interaction with fibronectin.
Circulating fibronectin, also known as opsonic alpha 2 surface binding glycoprotein or cold-insoluble globulin, modulates phagocytosis of tissue debris, fibrin microaggregates, and gelatin-coated colloids by the reticuloendothelial (RE) system. Opsonically active fibronectin has an actin binding site and a demonstrated in vitro affinity for actin. Since actin potentially released into blood and tissue fluids following tissue injury could complex with fibronectin, the present study evaluated the effect of actin on plasma opsonic activity and Kupffer cell phagocytosis. Intravenous injection of actin did not acutely decrease plasma immunoreactive fibronectin levels although fibronectin levels increased at 6, 12, and 24 hr postinjection. However, intravenous actin injection did depress RE phagocytic activity in vivo as measured by decreased blood clearance of test colloid and impaired hepatic uptake of colloid particles as well as retention of the particles in the circulation. In vitro, preincubation of plasma with actin depressed the opsonic activity of plasma with respect to its ability to support phagocytosis, but such treatment of plasma did not alter the detection of fibronectin by immunoassay. Utilizing purified fibronectin with demonstrated opsonic activity, it was also observed that actin interaction with fibronectin would block its biological ability to enhance phagocytosis. This effect appeared to be mediated at the humoral level, since no direct depressant effect of actin on Kupffer cell function was observed. Thus, actin, if released into the blood following injury, may contribute to bioassayable opsonic fibronectin deficiency and phagocytic dysfunction, but this disturbance would remain undetectable by immunoassay of fibronectin levels.
D000199:Actins / Q000494:pharmacology*; D000818:Animals; D005353:Fibronectins / Q000097:blood* / Q000276:immunology; D007728:Kupffer Cells / Q000276:immunology / Q000648:ultrastructure; D008099:Liver / Q000276:immunology; D008297:Male; D008854:Microscopy, Electron; D012157:Mononuclear Phagocyte System / Q000187:drug effects*; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000199:Actins; D005353:Fibronectins; D009895:Opsonin Proteins