Fibronectin inhibits the cytotoxic effect 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.
Baluna
R
R
Department of Microbiology, University of Texas Southwestern Medical Center at Dallas 75235-8576, USA.
Ghetie
V
V
Oppenheimer-Marks
N
N
Vitetta
E S
ES
D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D012276:Ricin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D013499:Surface Properties / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology / Q000187:drug effects
D005353:Fibronectins; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D012276:Ricin; D013936:Thymidine