Clearance of microparticulate fibrin by the reticuloendothelial system has been long recognized as a defense mechanism against intravascular fibrin deposition (1, 2). In general this has been assumed to be part of the relatively nonspecific phagocytic process whereby the reticuloendothelial system removes other microparticulate material such as bacteria, from the circulation. Numerous in vitro studies (3-7) have documented the fact that before formation of particulate fibrin, fibrin may exist in a soluble form, generally when in a soluble complex with fibrinogen, and/or fibrin degradation products (5-7). Recently we have demonstrated that soluble macromolecular complexes consisting of known ratios of fibrinogen and fibrin which were formed in vitro, remain soluble when injected into rabbits (7). These complexes also had impaired clearance from blood during reticuloendothelial system blockade with Thorotrast. In nonblockaded animals, the blood tl/2 of the fibrinogen/fibrin complex was less than 1 h. The results indicated that in part reticuloendothelial system uptake of fibrin depended on specific binding of soluble fibrin, before microparticle formation and phagocytosis. Specificity for fibrin was suggested, because in the same Thorotrast model we were unable to demonstrate impaired clearance of fibrinogen degradation product D (8), and intact fibrinogen had a normal blood tV2. Removal of soluble fibrinogen/fibrin complexes is of pathophysiological significance because of the clear, frequent clinical association of these complexes with intravascular coagulation (9-12), in contrast to the very rare demonstration of circulating microparticulate fibrin.To explore further the soluble fibrin-reticuloendothelial system interaction, and a possible surface receptor, in the present report, isolated peritoneal macrophages have been studied for their ability to bind soluble fibrin, fibrinogen, and other fibrinogen derivatives. Materials and MethodsFibrinogen and Derivatives. Human fibrinogen fraction I-4 was purified by the method of Blomback and Blomback (13) to ->95% clottability. Fibrinogen was labeled with ~31I or ~25I by the method of McFarlane (14) with -<0.5 atoms iodine/mole fibrinogen and >-94% radioactive clottabilo ity. The radiolabeled fibrinogen (F) 1 was converted to fibrin (f) by thrombin and the resultant clot * Supported by NIH Specialized Center of Research in Thrombosis grant no. HL-14147.
The solid-phase immune electron microscopy-double-antibody technique, which takes less than 1 h to perform, was applied as a rapid, sensitive, and specific diagnostic tool in the demonstration of papovavirus particles. BK virus propagated in 82C human skin fibroblasts and a monospecific high-titer immune serum to BK virus were used to establish the test procedure. When Formvar-carbon-coated grids were treated with appropriately diluted antibody, a 28-fold increase of virus particles per square micrometer was observed. Viewing of the virus particles was facilitated by the addition of a second "decorator" antibody. BK virus preparations at concentrations of 10(2) to 10(3) PFU/ml could be detected by this technique. There was no cross-reaction with mouse polyomavirus.
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