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Kupffer cells promote lead nitrate-induced hepatocyte apoptosis via oxidative stress.

Pagliara P, Carlà EC, Caforio S, Chionna A, Massa S, Abbro L, Dini L - Comp Hepatol (2003)

Bottom Line: RESULTS: The in vivo hepatic apoptosis, induced by Pb(NO3)2 was prevented by a pre-treatment with gadolinium chloride (GdCl3), a Kupffer cells toxicant, that suppresses Kupffer cell activity and reduces to a half the apoptotic rate.In addition, in vivo Pb(NO3)2 administration deprives hepatocytes of reduced glutathione, whereas the loss of this important oxidation-preventing agent is considerably mitigated or abolished by pre-treatment with GdCl3.CONCLUSION: Pb(NO3)2 has, at most, a direct necrotic (but not apoptogenic) effect on hepatocytes and HepG2 cells, giving a clue about the regulatory role of Kupffer cells in the induction of liver apoptosis after a single Pb(NO3)2 injection without pre-treatment with GdCl3, probably via secreting soluble factors that trigger oxidative stress in target cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Science and Biological and Environmental Technologies, University of Lecce, via per Monteroni, Lecce, Italy. luciana.dini@unile.it

ABSTRACT
BACKGROUND: Apoptosis and its modulation are crucial factors for the maintenance of liver health, allowing hepatocytes to die without provoking a potential harmful inflammatory response through a tightly controlled and regulated process. Since Kupffer cells play a key role in the maintenance of liver function, the aim of this study was to verify whether Kupffer cells are involved in the induction of liver apoptosis after i.v. injection of Pb(NO3)2 likely by secretion mechanisms. RESULTS: The in vivo hepatic apoptosis, induced by Pb(NO3)2 was prevented by a pre-treatment with gadolinium chloride (GdCl3), a Kupffer cells toxicant, that suppresses Kupffer cell activity and reduces to a half the apoptotic rate. In addition, in vivo Pb(NO3)2 administration deprives hepatocytes of reduced glutathione, whereas the loss of this important oxidation-preventing agent is considerably mitigated or abolished by pre-treatment with GdCl3. However, incubation of isolated hepatocytes and Kupffer cells and HepG2 cells with Pb(NO3)2 for 24 hours induced necrotic but not apoptotic cells. Apoptosis of hepatocytes and HepG2 cells was observed only after the addition of conditioned medium obtained from Kupffer cells cultured for 24 hours with Pb(NO3)2, thus indicating the secretion of soluble mediators of apoptosis by Kupffer cells. Apoptosis in the HepG2 cells was observed upon 24-hours incubation of HepG2 cells with 1 mM buthionine sulfoximine, a glutathione depleting agent, thus showing that there is an oxidative apoptogenic pathway in HepG2 cells. CONCLUSION: Pb(NO3)2 has, at most, a direct necrotic (but not apoptogenic) effect on hepatocytes and HepG2 cells, giving a clue about the regulatory role of Kupffer cells in the induction of liver apoptosis after a single Pb(NO3)2 injection without pre-treatment with GdCl3, probably via secreting soluble factors that trigger oxidative stress in target cells.

No MeSH data available.


Related in: MedlinePlus

Light micrographs of Hep G2 cells.(a) control untreated cells. (b) HepG2 cells were incubated for 24 hours with conditioned medium from Kupffer cells incubated 24 hours with Pb(NO3)2. Apoptotic cells are indicated by arrows. They appear with modified shape, i.e., elongated or pear-like, and the nucleus is more stained. Haematoxylin-eosin staining. Bar = 10 μm.
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Figure 4: Light micrographs of Hep G2 cells.(a) control untreated cells. (b) HepG2 cells were incubated for 24 hours with conditioned medium from Kupffer cells incubated 24 hours with Pb(NO3)2. Apoptotic cells are indicated by arrows. They appear with modified shape, i.e., elongated or pear-like, and the nucleus is more stained. Haematoxylin-eosin staining. Bar = 10 μm.

Mentions: Extremely low apoptotic rates and high necrotic rates (especially for cells cultured with Pb(NO3)2) were measured for HepG2 cells incubated with Pb(NO3)2, Pb(C2H3O2)2 or KNO3 for up to 24 hours. Apoptosis was detected upon incubation with Kupffer cells CM (Table 6 and Fig. 4). CM collected from control Kupffer cells, or cells cultured for 24 hours with KNO3, was unable to induce apoptosis in HepG2 cells.


Kupffer cells promote lead nitrate-induced hepatocyte apoptosis via oxidative stress.

Pagliara P, Carlà EC, Caforio S, Chionna A, Massa S, Abbro L, Dini L - Comp Hepatol (2003)

Light micrographs of Hep G2 cells.(a) control untreated cells. (b) HepG2 cells were incubated for 24 hours with conditioned medium from Kupffer cells incubated 24 hours with Pb(NO3)2. Apoptotic cells are indicated by arrows. They appear with modified shape, i.e., elongated or pear-like, and the nucleus is more stained. Haematoxylin-eosin staining. Bar = 10 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC184445&req=5

Figure 4: Light micrographs of Hep G2 cells.(a) control untreated cells. (b) HepG2 cells were incubated for 24 hours with conditioned medium from Kupffer cells incubated 24 hours with Pb(NO3)2. Apoptotic cells are indicated by arrows. They appear with modified shape, i.e., elongated or pear-like, and the nucleus is more stained. Haematoxylin-eosin staining. Bar = 10 μm.
Mentions: Extremely low apoptotic rates and high necrotic rates (especially for cells cultured with Pb(NO3)2) were measured for HepG2 cells incubated with Pb(NO3)2, Pb(C2H3O2)2 or KNO3 for up to 24 hours. Apoptosis was detected upon incubation with Kupffer cells CM (Table 6 and Fig. 4). CM collected from control Kupffer cells, or cells cultured for 24 hours with KNO3, was unable to induce apoptosis in HepG2 cells.

Bottom Line: RESULTS: The in vivo hepatic apoptosis, induced by Pb(NO3)2 was prevented by a pre-treatment with gadolinium chloride (GdCl3), a Kupffer cells toxicant, that suppresses Kupffer cell activity and reduces to a half the apoptotic rate.In addition, in vivo Pb(NO3)2 administration deprives hepatocytes of reduced glutathione, whereas the loss of this important oxidation-preventing agent is considerably mitigated or abolished by pre-treatment with GdCl3.CONCLUSION: Pb(NO3)2 has, at most, a direct necrotic (but not apoptogenic) effect on hepatocytes and HepG2 cells, giving a clue about the regulatory role of Kupffer cells in the induction of liver apoptosis after a single Pb(NO3)2 injection without pre-treatment with GdCl3, probably via secreting soluble factors that trigger oxidative stress in target cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Science and Biological and Environmental Technologies, University of Lecce, via per Monteroni, Lecce, Italy. luciana.dini@unile.it

ABSTRACT
BACKGROUND: Apoptosis and its modulation are crucial factors for the maintenance of liver health, allowing hepatocytes to die without provoking a potential harmful inflammatory response through a tightly controlled and regulated process. Since Kupffer cells play a key role in the maintenance of liver function, the aim of this study was to verify whether Kupffer cells are involved in the induction of liver apoptosis after i.v. injection of Pb(NO3)2 likely by secretion mechanisms. RESULTS: The in vivo hepatic apoptosis, induced by Pb(NO3)2 was prevented by a pre-treatment with gadolinium chloride (GdCl3), a Kupffer cells toxicant, that suppresses Kupffer cell activity and reduces to a half the apoptotic rate. In addition, in vivo Pb(NO3)2 administration deprives hepatocytes of reduced glutathione, whereas the loss of this important oxidation-preventing agent is considerably mitigated or abolished by pre-treatment with GdCl3. However, incubation of isolated hepatocytes and Kupffer cells and HepG2 cells with Pb(NO3)2 for 24 hours induced necrotic but not apoptotic cells. Apoptosis of hepatocytes and HepG2 cells was observed only after the addition of conditioned medium obtained from Kupffer cells cultured for 24 hours with Pb(NO3)2, thus indicating the secretion of soluble mediators of apoptosis by Kupffer cells. Apoptosis in the HepG2 cells was observed upon 24-hours incubation of HepG2 cells with 1 mM buthionine sulfoximine, a glutathione depleting agent, thus showing that there is an oxidative apoptogenic pathway in HepG2 cells. CONCLUSION: Pb(NO3)2 has, at most, a direct necrotic (but not apoptogenic) effect on hepatocytes and HepG2 cells, giving a clue about the regulatory role of Kupffer cells in the induction of liver apoptosis after a single Pb(NO3)2 injection without pre-treatment with GdCl3, probably via secreting soluble factors that trigger oxidative stress in target cells.

No MeSH data available.


Related in: MedlinePlus