Fibronectin increases Trypanosoma cruzi amastigote binding to and uptake by murine macrophages and human monocytes

Abstract

Trypanosoma cruzi amastigotes present receptors for human fibronectin as indicated by the saturable binding of [125I]fibronectin to this form of the parasite. Scatchard analysis indicates that the number of fibronectin receptors per amastigote was 1.3 x 103 with a K(d) of approximately 2.3 nM. Addition of physiological concentrations of fibronectin to amastigote-macrophage cocultures significantly increased the binding of amastigotes to murine macrophages. This increase was evidenced in both the number of amastigotes bound to macrophages and the percentage of macrophages containing bound amastigotes. The uptake of amastigotes by either murine macrophages or human blood monocytes was also increased in the presence of exogenous fibronectin. The increase induced by fibronectin was blocked when amastigotes were pretreated with the RGDS tetrapeptide of the fibronectin cell attachment site. Furthermore, the ability of fibronectin to enhance amastigote binding to and uptake by macrophages was inhibited by the F(ab')2 fragment of anti-fibronectin immunoglobulin G (IgG) but not by an irrelevant anti-human IgG F(ab')2 fragment. Pretreatment of either amastigotes or macrophages with fibronectin also resulted in a significant increase in amastigote binding to and uptake by macrophages. These results suggest that fibronectin may play a role in facilitating the attachment and ingestion of T. cruzi amastigotes by macrophages and monocytes in chagasic tissue lesions.