TGFβ1 increases microglia-mediated engulfment of apoptotic cells via upregulation of the milk fat globule-EGF factor 8

Glia ◽  
2014 ◽  
Vol 63 (1) ◽  
pp. 142-153 ◽  
Author(s):  
Björn Spittau ◽  
Jennifer Rilka ◽  
Elsa Steinfath ◽  
Tanja Zöller ◽  
Kerstin Krieglstein
Keyword(s):  
Milk Fat ◽  
Apoptotic Cells ◽  
Milk Fat Globule ◽  
Fat Globule

scholarly journals HMGB1 inhibits macrophage activity in efferocytosis through binding to the αvβ3-integrin

2010 ◽  
Vol 299 (6) ◽  
pp. C1267-C1276 ◽  
Author(s):  
Arnaud Friggeri ◽  
Yanping Yang ◽  
Sami Banerjee ◽  
Yong-Jun Park ◽  
Gang Liu ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Milk Fat ◽  
High Mobility ◽  
Inhibitory Effect ◽  
Αvβ3 Integrin ◽  
Apoptotic Cells ◽  
Macrophage Activity ◽  
Erk Phosphorylation ◽  
Milk Fat Globule ◽  
Fat Globule

Phagocytosis of apoptotic cells is critical to resolution of inflammation. High mobility group box 1 protein (HMGB1), a mediator of inflammation, has been shown to diminish phagocytosis through binding to phosphatidylserine (PS) exposed on the surface of apoptotic neutrophils. However, it is currently unknown whether HMGB1 also modulates the activity of receptors involved in PS recognition on the surface of phagocytes. In the present studies, we found that preincubation of macrophages with HMGB1 decreased their ability to engulf apoptotic neutrophils or thymocytes. Preincubation of macrophages with HMGB1 prevented the enhancement of efferocytosis resulting from exposure to milk fat globule EGF factor 8 (MFG-E8), an opsonin that bridges PS and αvβ3 as well as αvβ5-integrins on the surface of phagocytes. The inhibitory effect of HMGB1 on the phagocytic activity of macrophages was prevented by preincubation of HMGB1 with soluble αvβ3, but not with soluble αvβ5. HMGB1 colocalized with the β3-integrin on the cell membrane of macrophages and bound to soluble αvβ3, but not to soluble αvβ5. HMGB1 suppressed the interaction between MFG-E8 and αvβ3. HMGB1 also inhibited intracellular signaling events, including ERK phosphorylation and Rac-1 activation, which are activated in macrophages during phagocytosis of apoptotic cells. These results demonstrate that HMGB1 blocks αvβ3-dependent recognition and uptake of apoptotic cells.

scholarly journals Malignant Ovarian Tumors with Induced Expression of Carbonyl Reductase Show Spontaneous Regression

2012 ◽  
Vol 6 ◽  
pp. CMO.S9005 ◽  
Author(s):  
Hui Wang ◽  
Yoshihito Yokoyama ◽  
Shigeki Tsuchida ◽  
Hideki Mizunuma
Keyword(s):  
Ovarian Cancer ◽  
Milk Fat ◽  
Tumor Volume ◽  
Ovarian Cancer Cells ◽  
Control Group ◽  
Tumor Proliferation ◽  
Apoptotic Cells ◽  
Induction Group ◽  
Milk Fat Globule ◽  
Fat Globule

Background The present study investigated tumor proliferation in a tumor model using murine ovarian cancer cells with increased carbonyl reductase (CR) expression. Methods CR cDNA was transfected into murine T-Ag-MOSE ovarian cancer cells by lipofection. CR-transfected cells (CR induction group) or empty vector-treated cells (control group) were injected into the backs of 8-week-old nude mice at a concentration of 0.5 × 10 6 per 0.2 mL. Subsequent tumor proliferation in both groups was observed for 5 weeks. Results The control group showed an increase in tumor volume during the 5 weeks of observation. However, tumor volume in the CR induction group increased up to the second week but then decreased continuously until the fifth week of observation. The tumor growth curves for the two groups showed a significant difference (Mann-Whitney U test, P < 0.001). Histological and biochemical experiments were performed using tumor tissues isolated in the third week. Necrosis and inflammatory cell infiltration were noted for tumors in the CR induction group. Also, the number of apoptotic cells was significantly increased in the CR induction group compared with the control group ( P < 0.001). Milk fat globule EGF factor 8, an “eat-me” signal for phagocytes such as macrophages, was expressed extensively in the tumor cytoplasm and interstitial cells of the CR induction group, and engulfment of apoptotic cells by macrophages was observed. Vascular endothelial growth factor expression in tumors was notably decreased in the CR induction group compared with the control group. Conclusion Increased necrosis due to engulfing of apoptotic cells by phagocytes attracted by increased milk fat globule EGF factor 8 was considered to be the mechanism of spontaneous tumor regression in the CR induction group.

scholarly journals Milk Fat Globule Membrane Proteome and Micronutrients in the Milk Lipid Fraction: Insights into Milk Bioactive Compounds

Dairy ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 202-217
Author(s):  
Michele Manoni ◽  
Donata Cattaneo ◽  
Sharon Mazzoleni ◽  
Carlotta Giromini ◽  
Antonella Baldi ◽  
...  
Keyword(s):  
Milk Fat ◽  
Lipid Fraction ◽  
Value Added ◽  
Milk Lipid ◽  
Milk Fat Globule Membrane ◽  
Fat Globules ◽  
Milk Fat Globules ◽  
Milk Fat Globule ◽  
Fat Globule ◽  
Value Added Products

Milk lipids are composed of milk fat globules (MFGs) surrounded by the milk fat globule membrane (MFGM). MFGM protects MFGs from coalescence and enzymatic degradation. The milk lipid fraction is a “natural solvent” for macronutrients such as phospholipids, proteins and cholesterol, and micronutrients such as minerals and vitamins. The research focused largely on the polar lipids of MFGM, given their wide bioactive properties. In this review we discussed (i) the composition of MFGM proteome and its variations among species and phases of lactation and (ii) the micronutrient content of human and cow’s milk lipid fraction. The major MFGM proteins are shared among species, but the molecular function and protein expression of MFGM proteins vary among species and phases of lactation. The main minerals in the milk lipid fraction are iron, zinc, copper and calcium, whereas the major vitamins are vitamin A, β-carotene, riboflavin and α-tocopherol. The update and the combination of this knowledge could lead to the exploitation of the MFGM proteome and the milk lipid fraction at nutritional, biological or technological levels. An example is the design of innovative and value-added products, such as MFGM-supplemented infant formulas.

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