Faculty Bibliography

Fibronectin (Fn) is an adhesive glycoprotein that plays an important role in reticuloendothelial system functioning. Fn binds several macromolecules, it is found in cryoprecipitates obtained from patients with different diseases and it interacts in vitro with immune complexes. The interaction between Fn and polyclonal IgG was characterized by ligand affinity chromatography. After IgG was modified by attachment to a solid matrix or heat aggregation, it was able to interact with either soluble or immobilized Fn. The binding was highly influenced by ionic strength and pH. The estimated affinity constants were 3.0 x 10(6)/M when soluble Fn was applied to solid phase IgG and 2.3 x 10(7)/M when aggregated IgG interacted with immobilized Fn. The interaction may be relevant in situations in which immune complexes are involved

The primary structure of a 38 kDa heparin-binding domain from human plasma fibronectin has been determined. This domain contains 380 residues arranged in three type-III homology regions of approx. 90 residues each, and a 67-amino-acid C-terminal segment. This segment has been shown to be encoded by certain mRNA species only, due to alternative splicing [Kornblihtt, Vibe-Pedersen & Baralle (1984) Nucleic Acids Research 12, 5853-5868], and therefore represents a region of heterogeneity in fibronectin. Our data indicate that at least one of the constituent polypeptide chains contains this region.

Fibronectin has been shown to play an important role in reticuloendothelial system functioning as well as in neutrophil and fibroblast migration to tissue injury sites. Fibronectin binds several macromolecules including components of the acute phase response. We have studied the interaction of fibronectin with the amyloid P component (AP). This glycoprotein, closely related to C-reactive protein, is deposited together with amyloid fibrils and is also a normal constituent of human fibronectin, its whole tryptic digest, and isolated fragments; fibronectin was retained by immobilized AP in a molar ratio fibronectin:AP of 1:5.8. In this paper we localized the binding site for AP in a tryptic 31 kDa fragment, near the C-terminal end of the fibronectin molecule. A shorter fragment of 22 kDa starting at position 82 of the 31 kDa domain and containing all the disulfide bridges present in the 31 kDa domain did not bind to AP; therefore the active site appears to be located within the 81 N-terminal residues of the 31 kDa fragment. To further support this conclusion, reduction and alkylation of either fibronectin or the 31 kDa fragment had no effect on their binding properties.