Use of an in vitro system to study the effects of lead on astrocyte-endothelial cell interactions: A model for studying toxic injury to the blood-brain barrier

Ann Marie Gebhart, Gary William Goldstein

Research output: Contribution to journalArticle

Abstract

We investigated the effect of inorganic lead on the interaction of immature rat astrocytes and bovine adrenal endothelial cells. The two cell types were cultured alone and in coculture in the presence or absence of lead acetate for up to 1 week. A battery of cell specific markers was used for cell identification. Newborn Sprague-Dawley rat brain astrocytes were more sensitive than bovine adrenal endothelial cells to the cytotoxic effects of 10-50 μm lead acetate, as demonstrated by a decrease in cell number and by the presence of intracellular vacuoles and detached cells. The number of astrocytes decreased to 50% of control after 4 days in culture at a concentration of 10 μm lead. In contrast, a mitogenic effect of lead was observed on the endothelial cells at this concentration, with an increase in cell number to 110% of control. In coculture, the two cell types demonstrated a distinctive cellular organization and the astrocytes were less sensitive to the cytotoxic effects of lead than when they were cultured alone. A lead-enhanced induction of a neural capillary enzyme activity, γ-GTP, was detected histochemically in the coculture system. These results are consistent with a maturing of differentiating effect of the endothelial cells on the astrocytes, making them less susceptible to lead and mature enough to induce γ-GTP activity in the endothelial cells.

Original languageEnglish (US)
Pages (from-to)191-206
Number of pages16
JournalToxicology and Applied Pharmacology
Volume94
Issue number2
DOIs
StatePublished - Jun 30 1988
Externally publishedYes

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Poisons
Endothelial cells
Blood-Brain Barrier
Cell Communication
Astrocytes
Endothelial Cells
Coculture Techniques
Wounds and Injuries
Guanosine Triphosphate
Rats
Cell Count
Enzyme activity
Vacuoles
Sprague Dawley Rats
Cultured Cells
Brain
Lead
In Vitro Techniques
Enzymes
lead acetate

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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abstract = "We investigated the effect of inorganic lead on the interaction of immature rat astrocytes and bovine adrenal endothelial cells. The two cell types were cultured alone and in coculture in the presence or absence of lead acetate for up to 1 week. A battery of cell specific markers was used for cell identification. Newborn Sprague-Dawley rat brain astrocytes were more sensitive than bovine adrenal endothelial cells to the cytotoxic effects of 10-50 μm lead acetate, as demonstrated by a decrease in cell number and by the presence of intracellular vacuoles and detached cells. The number of astrocytes decreased to 50{\%} of control after 4 days in culture at a concentration of 10 μm lead. In contrast, a mitogenic effect of lead was observed on the endothelial cells at this concentration, with an increase in cell number to 110{\%} of control. In coculture, the two cell types demonstrated a distinctive cellular organization and the astrocytes were less sensitive to the cytotoxic effects of lead than when they were cultured alone. A lead-enhanced induction of a neural capillary enzyme activity, γ-GTP, was detected histochemically in the coculture system. These results are consistent with a maturing of differentiating effect of the endothelial cells on the astrocytes, making them less susceptible to lead and mature enough to induce γ-GTP activity in the endothelial cells.",
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AB - We investigated the effect of inorganic lead on the interaction of immature rat astrocytes and bovine adrenal endothelial cells. The two cell types were cultured alone and in coculture in the presence or absence of lead acetate for up to 1 week. A battery of cell specific markers was used for cell identification. Newborn Sprague-Dawley rat brain astrocytes were more sensitive than bovine adrenal endothelial cells to the cytotoxic effects of 10-50 μm lead acetate, as demonstrated by a decrease in cell number and by the presence of intracellular vacuoles and detached cells. The number of astrocytes decreased to 50% of control after 4 days in culture at a concentration of 10 μm lead. In contrast, a mitogenic effect of lead was observed on the endothelial cells at this concentration, with an increase in cell number to 110% of control. In coculture, the two cell types demonstrated a distinctive cellular organization and the astrocytes were less sensitive to the cytotoxic effects of lead than when they were cultured alone. A lead-enhanced induction of a neural capillary enzyme activity, γ-GTP, was detected histochemically in the coculture system. These results are consistent with a maturing of differentiating effect of the endothelial cells on the astrocytes, making them less susceptible to lead and mature enough to induce γ-GTP activity in the endothelial cells.

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