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Effects of pristane alone or combined with chloroquine on macrophage activation, oxidative stress, and TH1/TH2 skewness.

Ouyang Q, Huang Z, Wang Z, Chen X, Ni J, Lin L - J Immunol Res (2014)

Bottom Line: And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR.In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed.However, chloroquine supplementation showed a remarkable amelioration of these abnormalities.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road 34, Quanzhou, Fujian 362000, China.

ABSTRACT
We investigated the protective role of chloroquine against pristane-induced macrophage activation, oxidative stress, and Th1/Th2 skewness in C57BL/6J mice. Those mice were treated with pristane alone or combined with chloroquine. Hematological and biochemical parameters, macrophage phagocytic function, the oxidant/antioxidant index, cytokine for IFN-γ, TNF-α, IL-4, and IL-6, and the isotypes of IgG2a and IgG1 were determined. And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR. We found that pristane treatment for a period of 12 or 24 weeks triggered macrophage activation syndrome, characterized by hemophagocytosis in spleen and peripheral blood, enhanced lipid phagocytosis by peritoneal macrophages in vitro, erythropenia and leucopenia, increased anti-Smith, lactic dehydrogenase, triglyceride, and ferritin, as well as hypercytokinemia of IFN-γ, TNF-α, IL-4, and IL-6. In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed. However, chloroquine supplementation showed a remarkable amelioration of these abnormalities. Our data indicate that pristane administration induces macrophage activation, oxidative stress, and Th1/Th2 skewness, which can be attenuated by chloroquine.

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Related in: MedlinePlus

Hemophagocytosis, extramedullary hematopoiesis, and macrophage infiltration in liver and spleen. Hemophagocytosis (arrow), extramedullary hematopoiesis (arrow head) in liver and spleen were illustrated by HE staining ((a), (b)). The distribution and expression of F4/80 in liver and spleen were depicted with immunohistochemistry ((c), (d)) and western blotting (e), respectively. ×200; inset, ×400. CQ: chloroquine. Results were expressed as mean ± SE for eight animals. *P < 0.05 versus corresponding control mice, #P < 0.05 versus mice exposed to pristane for 12 weeks.
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fig1: Hemophagocytosis, extramedullary hematopoiesis, and macrophage infiltration in liver and spleen. Hemophagocytosis (arrow), extramedullary hematopoiesis (arrow head) in liver and spleen were illustrated by HE staining ((a), (b)). The distribution and expression of F4/80 in liver and spleen were depicted with immunohistochemistry ((c), (d)) and western blotting (e), respectively. ×200; inset, ×400. CQ: chloroquine. Results were expressed as mean ± SE for eight animals. *P < 0.05 versus corresponding control mice, #P < 0.05 versus mice exposed to pristane for 12 weeks.

Mentions: Control mice displayed normal structures of liver and spleen. And destroyed structure with lipid-vacuolated granulomas formation was observed after pristane injection. Splenomegaly (data not shown) and enhanced hemophagocytosis in liver and spleen were detected 12 weeks after pristane injection (Figure 1(b)), while, at 24 weeks after pristane injection, abundant extramedullary hematopoiesis including megakaryocytes, erythroid and granulocyte precursors was observed, with substantially increased megakaryocytes in spleen red pulp (Figure 1(d)). Alternatively, pristane induced an increased F4/80 protein expression in liver and spleen, as manifested by western blot analysis, which was further confirmed by IHC. Treatment with CQ for 12 weeks ameliorated hemophagocytosis and F4/80 positive macrophage infiltration.


Effects of pristane alone or combined with chloroquine on macrophage activation, oxidative stress, and TH1/TH2 skewness.

Ouyang Q, Huang Z, Wang Z, Chen X, Ni J, Lin L - J Immunol Res (2014)

Hemophagocytosis, extramedullary hematopoiesis, and macrophage infiltration in liver and spleen. Hemophagocytosis (arrow), extramedullary hematopoiesis (arrow head) in liver and spleen were illustrated by HE staining ((a), (b)). The distribution and expression of F4/80 in liver and spleen were depicted with immunohistochemistry ((c), (d)) and western blotting (e), respectively. ×200; inset, ×400. CQ: chloroquine. Results were expressed as mean ± SE for eight animals. *P < 0.05 versus corresponding control mice, #P < 0.05 versus mice exposed to pristane for 12 weeks.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4127244&req=5

fig1: Hemophagocytosis, extramedullary hematopoiesis, and macrophage infiltration in liver and spleen. Hemophagocytosis (arrow), extramedullary hematopoiesis (arrow head) in liver and spleen were illustrated by HE staining ((a), (b)). The distribution and expression of F4/80 in liver and spleen were depicted with immunohistochemistry ((c), (d)) and western blotting (e), respectively. ×200; inset, ×400. CQ: chloroquine. Results were expressed as mean ± SE for eight animals. *P < 0.05 versus corresponding control mice, #P < 0.05 versus mice exposed to pristane for 12 weeks.
Mentions: Control mice displayed normal structures of liver and spleen. And destroyed structure with lipid-vacuolated granulomas formation was observed after pristane injection. Splenomegaly (data not shown) and enhanced hemophagocytosis in liver and spleen were detected 12 weeks after pristane injection (Figure 1(b)), while, at 24 weeks after pristane injection, abundant extramedullary hematopoiesis including megakaryocytes, erythroid and granulocyte precursors was observed, with substantially increased megakaryocytes in spleen red pulp (Figure 1(d)). Alternatively, pristane induced an increased F4/80 protein expression in liver and spleen, as manifested by western blot analysis, which was further confirmed by IHC. Treatment with CQ for 12 weeks ameliorated hemophagocytosis and F4/80 positive macrophage infiltration.

Bottom Line: And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR.In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed.However, chloroquine supplementation showed a remarkable amelioration of these abnormalities.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road 34, Quanzhou, Fujian 362000, China.

ABSTRACT
We investigated the protective role of chloroquine against pristane-induced macrophage activation, oxidative stress, and Th1/Th2 skewness in C57BL/6J mice. Those mice were treated with pristane alone or combined with chloroquine. Hematological and biochemical parameters, macrophage phagocytic function, the oxidant/antioxidant index, cytokine for IFN-γ, TNF-α, IL-4, and IL-6, and the isotypes of IgG2a and IgG1 were determined. And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR. We found that pristane treatment for a period of 12 or 24 weeks triggered macrophage activation syndrome, characterized by hemophagocytosis in spleen and peripheral blood, enhanced lipid phagocytosis by peritoneal macrophages in vitro, erythropenia and leucopenia, increased anti-Smith, lactic dehydrogenase, triglyceride, and ferritin, as well as hypercytokinemia of IFN-γ, TNF-α, IL-4, and IL-6. In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed. However, chloroquine supplementation showed a remarkable amelioration of these abnormalities. Our data indicate that pristane administration induces macrophage activation, oxidative stress, and Th1/Th2 skewness, which can be attenuated by chloroquine.

Show MeSH
Related in: MedlinePlus