An experimental model for the study of the opsonic activity of fibronectin in the clearance of intravascular complexes.

An experimental model is described which provides direct evidence of endocytosis of complexes of a charged colloid (dextran sulphate or DS) and of plasma fibronectin (FN) by reticulo-endothelial (RE) cells. This supports previous suggestions that plasma FN acts as a non-immunologically mediated opsonin which effects the clearance of various kinds of circulating colloids and particles by RE cells. DS of molecular weight 500 000 forms FN-containing complexes in rat plasma in vitro and lowers plasma FN levels acutely and in a dose-related fashion when given parenterally to rats. The plasma changes are accompanied by deposition of DS (shown histochemically as metachromatic material) and of FN (shown by specific immunofluorescence) in an identical distribution within RE cells in rat liver and spleen. The protein and polysaccharide components of the complex are disposed of by RE cells at markedly different rates. The model thus also offers a means of studying the dynamics of catabolism of plasma FN by this 'scavenger' pathway. Possible further extensions of the model for other purposes are also discussed.

The role of fibronectin in the pathogenesis of antigen-induced arthritis in the rabbit.

Fibronectin (FN), a high molecular weight glycoprotein, is present in plasma and is a normal structural component of the synovium in the rabbit, as it is in man. FN is also involved in the sequence of changes seen in synovium in experimental antigen-induced arthritis. Its widespread distribution in inflamed synovia in the initial acute phase of induced arthritis probably merely reflects the presence of FN of plasma origin in serous exudates. In established experimental arthritis, FN co-distributes with fibrin, while in synovia undergoing organisation, FN is present intracellularly in several types of mesenchymal cells (suggesting local synthesis) and is deposited on immature collagen fibrils. However, it is no longer present when mature collagen is formed. The persistence of FN, along with fibrin, in inflamed joints, and its involvement in fibrosis, suggest that it may play a significant part in determining the chronicity of this form of experimental arthritis.

The significance of fibronectin in cryoprecipitation in rheumatoid arthritis and other diseases.

Fibronectin, a glycoprotein produced by mesenchymal cells, was present in 11 of 16 plasma cryoprecipitates and 12 of 14 synovial fluid (SF) cryoprecipitates. In some SF cryoprecipitates it was the major protein component. Fibronectin levels were related to the development of serum turbidity in the cold and fibronectin was involved in the development of cold turbidity induced by some charged polysaccharides in plasma, serum, and SF. It is suggested that fibronectin, which is synthesized by vascular endothelial cells and synovial lining cells, is involved in the development of some cryoprecipitates in patients with rheumatoid arthritis and other diseases.

Studies on reticulin. I: Serological and immunohistological investigations of the occurrence of collagen type III, fibronectin and the non-collagenous glycoprotein of Pras and Glynn in reticulin.

Collagen Type III, fibronectin and a non-collagenous reticulin component (NCRC) are all secretory products of fibroblasts and other mesenchymal cells. Antisera to human collagen III (isolated from the placenta) human plasma fibronectin, and NCRC (from spleen) have been used to examine possible antigenic relationships between these proteins both by serological studies and by comparison of the distribution of the proteins in various tissues using immunofluorescence. For other comparative purposes, the distribution of collagen and of reticulin in the same tissues was also sought using conventional histological methods. Serologically, the 3 antisera showed distinct specificities. However, when used on sections all 3 antisera gave closely similar staining patterns broadly resembling that of histological "reticulin", although minor differences were noted to be characteristic of the distribution of the respective antigens in certain tissues and in cell monolayers. The results support previous suggestions that histological "reticulin" is not a single entity but is a compound fibrous structure containing collagen Type III, fibronectin and at least 1 additional non-collagenous glycoprotein (NCRC).