Acute and Chronic Alcohol Exposure Impair the Phagocytosis of Apoptotic Cells and Enhance the Pulmonary Inflammatory Response

Boe, Devin M.; Richens, Tiffany R.; Horstmann, Sarah A.; Burnham, Ellen L.; Janssen, William J.; Henson, Peter M.; Moss, Marc; Vandivier, R. William

doi:10.1111/j.1530-0277.2010.01259.x

Cited by 47 publications

(33 citation statements)

References 52 publications

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“…Previous studies have shown that acute alcohol exposure attenuates macrophage efferocytosis (13). However, the exact molecular mechanisms underlying the effect remain largely unknown.…”

Section: Downregulation Of Mfg-e8 Gene Expression Is An Underlyingmentioning

confidence: 99%

“…Recently, Boé et al demonstrated that alcohol exposure results in impairment of efferocytosis, a process with characteristics that are distinct from engulfment of microorganisms (13). The effect of alcohol on inhibiting efferocytosis is partially mediated by RhoA-independent activation of ROCK (13). However, it remains unclear whether alcohol targets bridging molecules and subsequently disrupts efferocytosis.…”

Section: Mfg-e8 and Hmgb1 Are Involved In The Mechanism Underlying Almentioning

confidence: 99%

“…Acute alcohol exposure profoundly inhibits phagocytosis and killing of bacteria by macrophages (12). Recently, Boé et al demonstrated that alcohol exposure results in impairment of efferocytosis, a process with characteristics that are distinct from engulfment of microorganisms (13). The effect of alcohol on inhibiting efferocytosis is partially mediated by RhoA-independent activation of ROCK (13).…”

Section: Mfg-e8 and Hmgb1 Are Involved In The Mechanism Underlying Almentioning

confidence: 99%

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MFG-E8 and HMGB1 Are Involved in the Mechanism Underlying Alcohol-Induced Impairment of Macrophage Efferocytosis

Wang

Zhong

et al. 2013

Mol Med

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Efferocytosis is a unique phagocytic process for macrophages to remove apoptotic cells in inflammatory loci. This event is maintained by milk fat globule-EGF factor 8 (MFG-E8), but attenuated by high mobility group box 1 (HMGB1). Alcohol abuse causes injury and inflammation in multiple tissues. It alters efferocytosis, but precise molecular mechanisms for this effect remain largely unknown. Here, we showed that acute exposure of macrophages to alcohol (25 mmol/L) inhibited MFG-E8 gene expression and impaired efferocytosis. The effect was mimicked by hydrogen peroxide. Moreover, N-acetylcysteine (NAC), a potent antioxidant, blocked acute alcohol effect on inhibition of macrophage MFG-E8 gene expression and efferocytosis. In addition, recombinant MFG-E8 rescued the activity of alcohol-treated macrophages in efferocytosis. Together, the data suggest that acute alcohol exposure impairs macrophage efferocytosis via inhibition of MFG-E8 gene expression through a reactive oxygen species dependent mechanism. Alcohol has been found to suppress or exacerbate immune cell activities depending on the length of alcohol exposure. Thus, we further examined the role of chronic alcohol exposure on macrophage efferocytosis. Interestingly, treatment of macrophages with alcohol for seven days in vitro enhanced MFG-E8 gene expression and efferocytosis. However, chronic feeding of mice with alcohol caused increase in HMGB1 levels in serum. Furthermore, HMGB1 diminished efferocytosis by macrophages that were treated chronically with alcohol, suggesting that HMGB1 might attenuate the direct effect of chronic alcohol on macrophage efferocytosis in vivo. Therefore, we speculated that the balance between MFG-E8 and HMGB1 levels determines pathophysiological effects of chronic alcohol exposure on macrophage efferocytosis in vivo.

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“…Previous studies have shown that acute alcohol exposure attenuates macrophage efferocytosis (13). However, the exact molecular mechanisms underlying the effect remain largely unknown.…”

Section: Downregulation Of Mfg-e8 Gene Expression Is An Underlyingmentioning

confidence: 99%

Section: Mfg-e8 and Hmgb1 Are Involved In The Mechanism Underlying Almentioning

confidence: 99%

Section: Mfg-e8 and Hmgb1 Are Involved In The Mechanism Underlying Almentioning

confidence: 99%

See 1 more Smart Citation

MFG-E8 and HMGB1 Are Involved in the Mechanism Underlying Alcohol-Induced Impairment of Macrophage Efferocytosis

Wang

Zhong

et al. 2013

Mol Med

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“…Decreased immune functions associated with chronic alcohol consumption include granulopoiesis (8), tissue recruitment of neutrophils (9), TLR responsiveness of macrophages (10), and production of IL-12 (11). In addition, decreased macrophage phagocytosis (12)(13)(14) and an increased Th2 response (11,15,16) were demonstrated in alcoholics. A decrease in the Ag-presenting abilities of dendritic cells (17), perforin/granzyme expression, IFN-g production by conventional NK cells (18,19), and Th1/Th17 responses (20)(21)(22) also were reported.…”

Section: Cd14mentioning

confidence: 99%

“…Because such infections do not usually develop in healthy individuals, certain immune dysfunctions related to alcohol abuse are considered the underlying causes of the increased susceptibility of alcoholics to these infections. In fact, various host antibacterial immune functions are strongly influenced by chronic alcohol consumption (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Decreased immune functions associated with chronic alcohol consumption include granulopoiesis (8), tissue recruitment of neutrophils (9), TLR responsiveness of macrophages (10), and production of IL-12 (11).…”

Section: Cd14mentioning

confidence: 99%

M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria–Associated Sepsis in Alcoholics

Tsuchimoto

Asai

Tsuda

et al. 2015

The Journal of Immunology

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Chronic alcohol consumption markedly impairs host antibacterial defense against opportunistic infections. γ-irradiated NOD-SCID IL-2Rγnull mice inoculated with nonalcoholic PBMCs (control PBMC chimeras) resisted Klebsiella pneumonia and gut bacteria-associated sepsis, whereas the chimeras created with alcoholic PBMCs (alcoholic PBMC chimeras) were very susceptible to these infections. M1 monocytes (IL-12+IL-10−CD163−CD14+ cells), major effector cells in antibacterial innate immunity, were not induced by a bacterial Ag in alcoholic PBMC cultures, and M2b monocytes (CCL1+CD163+CD14+ cells), which predominated in alcoholic PBMCs, were shown to be inhibitor cells on the Ag-stimulated monocyte conversion from quiescent monocytes to M1 monocytes. CCL1, which functions to maintain M2b macrophage properties, was produced by M2b monocytes isolated from alcoholic PBMCs. These M2b monocytes reverted to quiescent monocytes (IL-12−IL-10−CCL1−CD163−CD14+ cells) in cultures supplemented with CCL1 antisense oligodeoxynucleotide, and the subsequent quiescent monocytes easily converted to M1 monocytes under bacterial Ag stimulation. Alcoholic PBMC chimeras treated with CCL1 antisense oligodeoxynucleotide were resistant against pulmonary infection by K. pneumoniae and sepsis stemming from enterococcal translocation. These results indicate that a majority of monocytes polarize to an M2b phenotype in association with alcohol abuse, and this polarization contributes to the increased susceptibility of alcoholics to gut and lung infections. Bacterial pneumonia and gut bacteria-associated sepsis, frequently seen in alcoholics, can be controlled through the polarization of macrophage phenotypes.

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Inhibition of miR‐103a‐3p suppresses lipopolysaccharide‐induced sepsis and liver injury by regulating FBXW7 expression

Zhou

Qin

2020

Cell Biology International

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Inflammation, apoptosis, and oxidative stress are involved in septic liver dysfunction. Herein, the role of miR‐103a‐3p/FBXW7 axis in lipopolysaccharides (LPS)‐induced septic liver injury was investigated in mice. Hematoxylin‐eosin staining was used to evaluate LPS‐induced liver injury. Quantitative real‐time polymerase chain reaction was performed to determine the expression of microRNA (miR) and messenger RNA, and western blot analysis was conducted to examine the protein levels. Dual‐luciferase reporter assay was used to confirm the binding between miR‐103a‐3p and FBXW7. Both annexin V‐fluoresceine isothiocyanate/propidium iodide staining and caspase‐3 activity were employed to determine cell apoptosis. First, miR‐103a‐3p was upregulated in the septic serum of mice and patients with sepsis, and miR‐103a‐3p was elevated in the septic liver of LPS‐induced mice. Then, interfering miR‐103a‐3p significantly decreased apoptosis by suppressing Bax expression and upregulating Bcl‐2 levels in LPS‐induced AML12 and LO2 cells, and septic liver of mice. Furthermore, inhibition of miR‐103a‐3p repressed LPS‐induced inflammation by downregulating the expression of tumor necrosis factor, interleukin 1β, and interleukin 6 in vitro and in vivo. Meanwhile, interfering miR‐103a‐3p obviously attenuated LPS‐induced overactivation of oxidation via promoting expression of antioxidative enzymes, including catalase, superoxide dismutase, and glutathione in vitro and in vivo. Moreover, FBXW7 was a target of miR‐103a‐3p, and overexpression of FBXW7 significantly ameliorated LPS‐induced septic liver injury in mice. Finally, knockdown of FBXW7 markedly reversed anti‐miR‐103a‐3p‐mediated suppression of septic liver injury in mice. In conclusion, interfering miR‐103a‐3p or overexpression of FBXW7 improved LPS‐induced septic liver injury by suppressing apoptosis, inflammation, and oxidative reaction.

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Acute and Chronic Alcohol Exposure Impair the Phagocytosis of Apoptotic Cells and Enhance the Pulmonary Inflammatory Response

Cited by 47 publications

References 52 publications

MFG-E8 and HMGB1 Are Involved in the Mechanism Underlying Alcohol-Induced Impairment of Macrophage Efferocytosis

MFG-E8 and HMGB1 Are Involved in the Mechanism Underlying Alcohol-Induced Impairment of Macrophage Efferocytosis

M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria–Associated Sepsis in Alcoholics

Inhibition of miR‐103a‐3p suppresses lipopolysaccharide‐induced sepsis and liver injury by regulating FBXW7 expression

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