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Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes.

Saja MF, Baudino L, Jackson WD, Cook HT, Malik TH, Fossati-Jimack L, Ruseva M, Pickering MC, Woollard KJ, Botto M - Cell Rep (2015)

Bottom Line: Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1(low) monocytes drop, while the number of bone marrow progenitors remains similar.We observed an increased crawling and retention of the Gr1(low) monocytes at the endothelial interface and a marked accumulation of CD68(+) macrophages in several organs.The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells.

View Article: PubMed Central - PubMed

Affiliation: Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.

No MeSH data available.


Related in: MedlinePlus

Tissue Accumulation of CD68+ Cells under P-407 Treatment(A) Representative photomicrographs of CD68 staining (brown) of PLP fixed liver, heart, and kidney sections after 7, 14, and 28 days of P-407 administration and after PBS treatment for 28 days. Magnification as indicated.(B) Quantitative analysis of CD68+ cells in (A) specimens showing accumulation of CD68+ macrophages in the P-407-treated animals. For liver and heart, data are expressed as mean percentage ± SE of the brown-stained area in a selected field/total field area (five different fields per section). For the kidney, data represent mean percentage ± SE of the brown-stained glomerular area/total glomerular area for 20 glomeruli per section. Values represent the mean ± SE of at least four mice per group. p value by unpaired t test is shown (∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001).(C) Representative images of the Ki-67 staining (green) and CD68 (red) of the sections (A) following 28 days of treatment with P-407 or PBS. Splenic sections were used as positive controls, and Ki-67+ cells are indicated with arrows. Scale bars, 75 μm.See also Figure S4.
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fig4: Tissue Accumulation of CD68+ Cells under P-407 Treatment(A) Representative photomicrographs of CD68 staining (brown) of PLP fixed liver, heart, and kidney sections after 7, 14, and 28 days of P-407 administration and after PBS treatment for 28 days. Magnification as indicated.(B) Quantitative analysis of CD68+ cells in (A) specimens showing accumulation of CD68+ macrophages in the P-407-treated animals. For liver and heart, data are expressed as mean percentage ± SE of the brown-stained area in a selected field/total field area (five different fields per section). For the kidney, data represent mean percentage ± SE of the brown-stained glomerular area/total glomerular area for 20 glomeruli per section. Values represent the mean ± SE of at least four mice per group. p value by unpaired t test is shown (∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001).(C) Representative images of the Ki-67 staining (green) and CD68 (red) of the sections (A) following 28 days of treatment with P-407 or PBS. Splenic sections were used as positive controls, and Ki-67+ cells are indicated with arrows. Scale bars, 75 μm.See also Figure S4.

Mentions: To extend the intravital microscopy findings to other organs, we then stained liver, heart, and kidney with an antibody against CD68, a widely used marker for tissue macrophages. The immunohistochemical quantification at different time points revealed a striking and gradually increasing accumulation of CD68+ cells in the P-407-injected animals compared to the PBS-treated controls (Figures 4A and 4B). F4/80 staining of the liver confirmed the increased presence of macrophages (Figure S4C). In agreement with the intravital findings, the number of CD68+ cells was already significantly increased 1 week after P-407 injections.


Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes.

Saja MF, Baudino L, Jackson WD, Cook HT, Malik TH, Fossati-Jimack L, Ruseva M, Pickering MC, Woollard KJ, Botto M - Cell Rep (2015)

Tissue Accumulation of CD68+ Cells under P-407 Treatment(A) Representative photomicrographs of CD68 staining (brown) of PLP fixed liver, heart, and kidney sections after 7, 14, and 28 days of P-407 administration and after PBS treatment for 28 days. Magnification as indicated.(B) Quantitative analysis of CD68+ cells in (A) specimens showing accumulation of CD68+ macrophages in the P-407-treated animals. For liver and heart, data are expressed as mean percentage ± SE of the brown-stained area in a selected field/total field area (five different fields per section). For the kidney, data represent mean percentage ± SE of the brown-stained glomerular area/total glomerular area for 20 glomeruli per section. Values represent the mean ± SE of at least four mice per group. p value by unpaired t test is shown (∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001).(C) Representative images of the Ki-67 staining (green) and CD68 (red) of the sections (A) following 28 days of treatment with P-407 or PBS. Splenic sections were used as positive controls, and Ki-67+ cells are indicated with arrows. Scale bars, 75 μm.See also Figure S4.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590546&req=5

fig4: Tissue Accumulation of CD68+ Cells under P-407 Treatment(A) Representative photomicrographs of CD68 staining (brown) of PLP fixed liver, heart, and kidney sections after 7, 14, and 28 days of P-407 administration and after PBS treatment for 28 days. Magnification as indicated.(B) Quantitative analysis of CD68+ cells in (A) specimens showing accumulation of CD68+ macrophages in the P-407-treated animals. For liver and heart, data are expressed as mean percentage ± SE of the brown-stained area in a selected field/total field area (five different fields per section). For the kidney, data represent mean percentage ± SE of the brown-stained glomerular area/total glomerular area for 20 glomeruli per section. Values represent the mean ± SE of at least four mice per group. p value by unpaired t test is shown (∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001).(C) Representative images of the Ki-67 staining (green) and CD68 (red) of the sections (A) following 28 days of treatment with P-407 or PBS. Splenic sections were used as positive controls, and Ki-67+ cells are indicated with arrows. Scale bars, 75 μm.See also Figure S4.
Mentions: To extend the intravital microscopy findings to other organs, we then stained liver, heart, and kidney with an antibody against CD68, a widely used marker for tissue macrophages. The immunohistochemical quantification at different time points revealed a striking and gradually increasing accumulation of CD68+ cells in the P-407-injected animals compared to the PBS-treated controls (Figures 4A and 4B). F4/80 staining of the liver confirmed the increased presence of macrophages (Figure S4C). In agreement with the intravital findings, the number of CD68+ cells was already significantly increased 1 week after P-407 injections.

Bottom Line: Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1(low) monocytes drop, while the number of bone marrow progenitors remains similar.We observed an increased crawling and retention of the Gr1(low) monocytes at the endothelial interface and a marked accumulation of CD68(+) macrophages in several organs.The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells.

View Article: PubMed Central - PubMed

Affiliation: Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.

No MeSH data available.


Related in: MedlinePlus