Fibronectin inhibits the cytotoxic effects of ricin A chain on endothelial cells

We have previously reported that after in vitro treatment with deglycosylated ricin A chain (dgRTA), human umbilical vein endothelial cells (HUVECs) undergo changes in morphology including cell rounding and disruption of monolayers. The present studies were carried out to determine whether these changes were related to the disruptions in endothelial cell (EC) interactions with the extracellular matrix. To this end, we examined the effect of dgRTA on HUVECs in the presence of fibronectin (Fn), an extracellular matrix protein, which plays a role in the maintenance of vascular integrity. The addition of exogenous Fn greatly inhibited dgRTA-mediated morphological changes in HUVEC monolayers, dgRTA-mediated inhibition of [³H]thymidine incorporation in HUVECs and the binding of ¹²⁵I-dgRTA to HUVECs. Should the same phenomenon occur with RTA-based immunotoxins (ITs) in vivo, this might shed light on the development of dgRTA-mediated vascular leak syndrome (VLS) during IT therapy and provide new insights into how to decrease this toxicity in patients.