Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells

Implications for vascular leak syndrome

Ana María Soler-Rodríguez, Maria Ana Ghetie, Nancy Oppenheimer-Marks, Jonathan W. Uhr, Ellen S. Vitetta

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

The results of Phase I/II clinical trials indicate that ricin A-chain-containing immunotoxins cause vascular leak syndrome, characterized by hypoalbuminemia with resultant weight gain and edema. Vascular leak syndrome may be a dose-limiting factor during treatment with ricin A-chain-containing immunotoxins. In this report, we determined the effect of ricin A-chain and ricin A-chain-containing immunotoxins on human umbilical vein endothelial cells with the aim of developing an in vitro model to study vascular leak syndrome. The major findings of our study are: (1) Human umbilical vein endothelial cells undergo rapid and dramatic changes in morphology after treatment with ricin A-chain and ricin A-chain-containing immunotoxins. These changes include rounding of the cells and, eventually, the formation of gaps between them. (2) The permeability of human umbilical vein endothelial cell monolayers to passage of molecules increases after exposure to ricin A-chain or ricin A-chain-containing immunotoxins and this is consistent with the morphologic changes. (3) Human umbilical vein endothelial cells bind 125I-rRTA in a dose-dependent manner but binding is not specific. (4) Human umbilical vein endothelial cells are moderately more sensitive to ricin A-chain-induced inhibition of protein synthesis and proliferation than simian virus-transformed mouse endothelial cells. (5) The morphologic changes are observed 1 h after exposure to the toxins, whereas inhibition of protein synthesis is not detectable until 4 h after a similar exposure. The in vitro model represents a first step in dissecting the complex events which occur in cancer patients who develop vascular leak syndrome after treatment with ricin A-chain-containing immunotoxins.

Original languageEnglish (US)
Pages (from-to)227-234
Number of pages8
JournalExperimental Cell Research
Volume206
Issue number2
StatePublished - 1993

Fingerprint

Ricin
Immunotoxins
Endothelial Cells
Human Umbilical Vein Endothelial Cells
Blood Vessels
Hypoalbuminemia
Phase II Clinical Trials
Clinical Trials, Phase I
Weight Gain
Permeability
Edema
Proteins
Therapeutics
Viruses

ASJC Scopus subject areas

  • Cell Biology

Cite this

Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells : Implications for vascular leak syndrome. / Soler-Rodríguez, Ana María; Ghetie, Maria Ana; Oppenheimer-Marks, Nancy; Uhr, Jonathan W.; Vitetta, Ellen S.

In: Experimental Cell Research, Vol. 206, No. 2, 1993, p. 227-234.

Research output: Contribution to journalArticle

Soler-Rodríguez, Ana María ; Ghetie, Maria Ana ; Oppenheimer-Marks, Nancy ; Uhr, Jonathan W. ; Vitetta, Ellen S. / Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells : Implications for vascular leak syndrome. In: Experimental Cell Research. 1993 ; Vol. 206, No. 2. pp. 227-234.
@article{dd9b116593104c36977a71e3d153578d,
title = "Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells: Implications for vascular leak syndrome",
abstract = "The results of Phase I/II clinical trials indicate that ricin A-chain-containing immunotoxins cause vascular leak syndrome, characterized by hypoalbuminemia with resultant weight gain and edema. Vascular leak syndrome may be a dose-limiting factor during treatment with ricin A-chain-containing immunotoxins. In this report, we determined the effect of ricin A-chain and ricin A-chain-containing immunotoxins on human umbilical vein endothelial cells with the aim of developing an in vitro model to study vascular leak syndrome. The major findings of our study are: (1) Human umbilical vein endothelial cells undergo rapid and dramatic changes in morphology after treatment with ricin A-chain and ricin A-chain-containing immunotoxins. These changes include rounding of the cells and, eventually, the formation of gaps between them. (2) The permeability of human umbilical vein endothelial cell monolayers to passage of molecules increases after exposure to ricin A-chain or ricin A-chain-containing immunotoxins and this is consistent with the morphologic changes. (3) Human umbilical vein endothelial cells bind 125I-rRTA in a dose-dependent manner but binding is not specific. (4) Human umbilical vein endothelial cells are moderately more sensitive to ricin A-chain-induced inhibition of protein synthesis and proliferation than simian virus-transformed mouse endothelial cells. (5) The morphologic changes are observed 1 h after exposure to the toxins, whereas inhibition of protein synthesis is not detectable until 4 h after a similar exposure. The in vitro model represents a first step in dissecting the complex events which occur in cancer patients who develop vascular leak syndrome after treatment with ricin A-chain-containing immunotoxins.",
author = "Soler-Rodr{\'i}guez, {Ana Mar{\'i}a} and Ghetie, {Maria Ana} and Nancy Oppenheimer-Marks and Uhr, {Jonathan W.} and Vitetta, {Ellen S.}",
year = "1993",
language = "English (US)",
volume = "206",
pages = "227--234",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells

T2 - Implications for vascular leak syndrome

AU - Soler-Rodríguez, Ana María

AU - Ghetie, Maria Ana

AU - Oppenheimer-Marks, Nancy

AU - Uhr, Jonathan W.

AU - Vitetta, Ellen S.

PY - 1993

Y1 - 1993

N2 - The results of Phase I/II clinical trials indicate that ricin A-chain-containing immunotoxins cause vascular leak syndrome, characterized by hypoalbuminemia with resultant weight gain and edema. Vascular leak syndrome may be a dose-limiting factor during treatment with ricin A-chain-containing immunotoxins. In this report, we determined the effect of ricin A-chain and ricin A-chain-containing immunotoxins on human umbilical vein endothelial cells with the aim of developing an in vitro model to study vascular leak syndrome. The major findings of our study are: (1) Human umbilical vein endothelial cells undergo rapid and dramatic changes in morphology after treatment with ricin A-chain and ricin A-chain-containing immunotoxins. These changes include rounding of the cells and, eventually, the formation of gaps between them. (2) The permeability of human umbilical vein endothelial cell monolayers to passage of molecules increases after exposure to ricin A-chain or ricin A-chain-containing immunotoxins and this is consistent with the morphologic changes. (3) Human umbilical vein endothelial cells bind 125I-rRTA in a dose-dependent manner but binding is not specific. (4) Human umbilical vein endothelial cells are moderately more sensitive to ricin A-chain-induced inhibition of protein synthesis and proliferation than simian virus-transformed mouse endothelial cells. (5) The morphologic changes are observed 1 h after exposure to the toxins, whereas inhibition of protein synthesis is not detectable until 4 h after a similar exposure. The in vitro model represents a first step in dissecting the complex events which occur in cancer patients who develop vascular leak syndrome after treatment with ricin A-chain-containing immunotoxins.

AB - The results of Phase I/II clinical trials indicate that ricin A-chain-containing immunotoxins cause vascular leak syndrome, characterized by hypoalbuminemia with resultant weight gain and edema. Vascular leak syndrome may be a dose-limiting factor during treatment with ricin A-chain-containing immunotoxins. In this report, we determined the effect of ricin A-chain and ricin A-chain-containing immunotoxins on human umbilical vein endothelial cells with the aim of developing an in vitro model to study vascular leak syndrome. The major findings of our study are: (1) Human umbilical vein endothelial cells undergo rapid and dramatic changes in morphology after treatment with ricin A-chain and ricin A-chain-containing immunotoxins. These changes include rounding of the cells and, eventually, the formation of gaps between them. (2) The permeability of human umbilical vein endothelial cell monolayers to passage of molecules increases after exposure to ricin A-chain or ricin A-chain-containing immunotoxins and this is consistent with the morphologic changes. (3) Human umbilical vein endothelial cells bind 125I-rRTA in a dose-dependent manner but binding is not specific. (4) Human umbilical vein endothelial cells are moderately more sensitive to ricin A-chain-induced inhibition of protein synthesis and proliferation than simian virus-transformed mouse endothelial cells. (5) The morphologic changes are observed 1 h after exposure to the toxins, whereas inhibition of protein synthesis is not detectable until 4 h after a similar exposure. The in vitro model represents a first step in dissecting the complex events which occur in cancer patients who develop vascular leak syndrome after treatment with ricin A-chain-containing immunotoxins.

UR - http://www.scopus.com/inward/record.url?scp=0027219786&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027219786&partnerID=8YFLogxK

M3 - Article

VL - 206

SP - 227

EP - 234

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 2

ER -