Signals of vagal circuits engaging with AKT1 in α7 nAChR+CD11b+ cells lessen E. coli and LPS-induced acute inflammatory injury

Zhao, Chengcheng; Yang, Xi; Su, Emily M.; Huang, Yuanyuan; Li, Ling; Matthay, Michael A.; Su, Xiao

doi:10.1038/celldisc.2017.9

Cited by 35 publications

(38 citation statements)

References 68 publications

(96 reference statements)

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“…In accordance to previous studies 54 , following LPS challenge the proportion of α7nAChR + CD11b + cells were greatly increased, which might be recruited from spleen or bone marrows. However, our multicolor flow cytometry studies revealed that the main fraction of these α7nAChR + cells were alveolar and interstitial macrophages and monocytes.…”

Section: Discussionsupporting

confidence: 92%

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High-fat diet-induced obesity affects alpha 7 nicotine acetylcholine receptor expressions in mouse lung myeloid cells

Zhu

et al. 2020

Sci Rep

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Ample evidence indicates that obesity causes dysfunctions in the lung. Previous studies also show that cholinergic anti-inflammatory pathways play crucial roles in obesity-induced chronic inflammation via α7 nicotinic acetylcholine receptor (α7nAChR) signaling. However, it remains unclear whether and how obesity affects the expressions of α7nAChR in myeloid cells in the lung. To address this question, we treated regular chow diet-fed mice or high-fat diet induced obese mice with lipopolysaccharide (LPS) or vehicle via endotracheal injections. By using a multicolor flow cytometry approach to analyze and characterize differential cell subpopulations and α7nAChR expressions, we find no detectable α7nAChR in granulocytes, monocytes and alveolar macrophages, and low expression levels of α7nAChR were detected in interstitial macrophages. Interestingly, we find that a challenge with LPS treatment significantly increased expression levels of α7nAChR in monocytes, alveolar and interstitial macrophages. Meanwhile, we observed that the expression levels of α7nAChR in alveolar and interstitial macrophages in high-fat diet induced obese mice were lower than regular chow diet-fed mice challenged by the LPS. Together, our findings indicate that obesity alters the expressions of α7nAChR in differential lung myeloid cells.

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Section: Discussionsupporting

confidence: 92%

“…Liegeois et al . 57 pointed out that a percentage of the lung interstitial macrophages could be supplemented by the monocytes in the blood circulation, we presumed that α7nAChR + interstitial macrophages may be derived from α7nAChR + monocytes, which probably recruited from the spleen after LPS challenge 54 .…”

Section: Discussionmentioning

confidence: 91%

High-fat diet-induced obesity affects alpha 7 nicotine acetylcholine receptor expressions in mouse lung myeloid cells

Zhu

et al. 2020

Sci Rep

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“…The methods used to passage, store, amplify, and quantify the bacteria have been described [6]. Acute lung injury was induced by instilling E. coli into the lungs of mice [6].…”

Section: E Coli Pneumonia Modelmentioning

confidence: 99%

“…Vagal sensory nerve endings, brain integration centers, acetylcholine, and α7 nicotinic acetylcholine receptor (nAChR)-expressing cells form a pulmonary parasympathetic inflammatory reflex to regulate lung infection and inflammation [4,5]. This machinery also synergizes with the spleen (as a functional hub of the cholinergic anti-inflammatory pathway) to fine-tune lung infection and immunity [6]. Clinical studies have demonstrated that vagus nerve stimulation targeting the inflammatory reflex modulates the TNF production and reduces inflammation in rheumatoid arthritis [7].…”

Section: Introductionmentioning

confidence: 99%

Vagal α7nAChR signaling regulates α7nAChR+Sca1+ cells during lung injury repair

Chen

Song

et al. 2020

Stem Cell Res Ther

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Background: The distal airways of the lung and bone marrow are innervated by the vagus nerve. Vagal α7nAChR signaling plays a key role in regulating lung infection and inflammation; however, whether this pathway regulates α7nAChR + Sca1 + cells during lung injury repair remains unknown. We hypothesized that vagal α7nAChR signaling controls α7nAChR + Sca1 + cells, which contribute to the resolution of lung injury. Methods: Pneumonia was induced by intratracheal challenge with E. coli. The bone marrow mononuclear cells (BM-MNCs) were isolated from the bone marrow of pneumonia mice for immunofluorescence. The bone marrow, blood, BAL, and lung cells were isolated for flow cytometric analysis by labeling with anti-Sca1, VE-cadherin, p-Akt1, or Flk1 antibodies. Immunofluorescence was also used to examine the coexpression of α7nAChR, VE-cadherin, and p-Akt1. Sham, vagotomized, α7nAChR knockout, and Akt1 knockout mice were infected with E. coli to study the regulatory role of vagal α7nAChR signaling and Akt1 in Sca1 + cells. Results: During pneumonia, BM-MNCs were enriched with α7nAChR + Sca1 + cells, and this cell population proliferated. Transplantation of pneumonia BM-MNCs could mitigate lung injury and increase engraftment in recipient pneumonia lungs. Activation of α7nAChR by its agonist could boost α7nAChR + Sca1 + cells in the bone marrow, peripheral blood, and bronchoalveolar lavage (BAL) in pneumonia. Immunofluorescence revealed that α7nAChR, VE-cadherin, and p-Akt1 were coexpressed in the bone marrow cells. Vagotomy could reduce α7nAChR + VE-cadherin + and VE-cadherin + p-Akt1 + cells in the bone marrow in pneumonia. Knockout of α7nAChR reduced VE-cadherin + cells and p-Akt1 + cells in the bone marrow. Deletion of Akt1 reduced Sca1 + cells in the bone marrow and BAL. More importantly, 91.3 ± 4.9% bone marrow and 77.8 ± 4.9% lung α7nAChR + Sca1 + VE-cadherin + cells expressed Flk1, which is a key marker of endothelial progenitor cells (EPCs). Vagotomy reduced α7nAChR + Sca1 + VE-cadherin + p-Akt1 + cells in the bone marrow and lung from pneumonia mice. Treatment with cultured EPCs reduced ELW compared to PBS treatment in E. coli pneumonia mice at 48 h. The ELW was further reduced by treatment with EPCs combining with α7nAChR agonist-PHA568487 compared to EPC treatments only.

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“…In sepsis caused by gram-negative bacteria, binding of LPS to the CD14 membrane receptor leads to excessive activation of monocytes and macrophages [10]. LPS stimulation also causes activation of NF-kB and p38 mitogen-activated protein kinase (p38 MAPK) [11]. Activated monocytes and macrophages release large amounts of TNF-α, the main mediator of sepsis.…”

Section: Introductionmentioning

confidence: 99%

Activation of α7 Nicotinic Acetylcholine Receptor Upregulates HLA-DR and Macrophage Receptors: Potential Role in Adaptive Immunity and in Preventing Immunosuppression

et al. 2020

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Immune response during sepsis is characterized by hyper-inflammation followed by immunosuppression. The crucial role of macrophages is well-known for both septic stages, since they are involved in immune homeostasis and inflammation, their dysfunction being implicated in immunosuppression. The cholinergic anti-inflammatory pathway mediated by macrophage α7 nicotinic acetylcholine receptor (nAChR) represents possible drug target. Although α7 nAChR activation on macrophages reduces the production of proinflammatory cytokines, the role of these receptors in immunological changes at the cellular level is not fully understood. Using α7 nAChR selective agonist PNU 282,987, we investigated the influence of α7 nAChR activation on the expression of cytokines and, for the first time, of the macrophage membrane markers: cluster of differentiation 14 (CD14), human leukocyte antigen-DR (HLA-DR), CD11b, and CD54. Application of PNU 282,987 to THP-1Mϕ (THP-1 derived macrophages) cells led to inward ion currents and Ca2+ increase in cytoplasm showing the presence of functionally active α7 nAChR. Production of cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 was estimated in classically activated macrophages (M1) and treatment with PNU 282,987 diminished IL-10 expression. α7 nAChR activation on THP-1Mϕ, THP-1M1, and monocyte-derived macrophages (MDMs) increased the expression of HLA-DR, CD54, and CD11b molecules, but decreased CD14 receptor expression, these effects being blocked by alpha (α)-bungarotoxin. Thus, PNU 282,987 enhances the macrophage-mediated immunity via α7 nAChR by regulating expression of their membrane receptors and of cytokines, both playing an important role in preventing immunosuppressive states.

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Signals of vagal circuits engaging with AKT1 in α7 nAChR+CD11b+ cells lessen E. coli and LPS-induced acute inflammatory injury

Cited by 35 publications

References 68 publications

High-fat diet-induced obesity affects alpha 7 nicotine acetylcholine receptor expressions in mouse lung myeloid cells

High-fat diet-induced obesity affects alpha 7 nicotine acetylcholine receptor expressions in mouse lung myeloid cells

Vagal α7nAChR signaling regulates α7nAChR+Sca1+ cells during lung injury repair

Activation of α7 Nicotinic Acetylcholine Receptor Upregulates HLA-DR and Macrophage Receptors: Potential Role in Adaptive Immunity and in Preventing Immunosuppression

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