Neutrophil transcriptional profile changes during transit from bone marrow to sites of inflammation

Lakschevitz, Flavia S.; Visser, Michelle B.; Sun, Cong; Glogauer, Michael

doi:10.1038/cmi.2014.37

Cited by 50 publications

(51 citation statements)

References 62 publications

(102 reference statements)

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“…We propose that some systemic compensatory responses may have occurred (i.e., upregulation of transcriptional networks related to the BM IS) during the recovery period following the reconstitution of C57 mice with the KO BM, as is often the case with transgenic manipulations, and as suggested above. In addition, studies have shown that BMderived immune cells can show transitions in transcriptional networks when moving from bone to blood, as is the case with neutrophils (14). It would be interesting to determine how the BM SNS regulates these transitions in specific immune cells.…”

Section: Discussionmentioning

confidence: 98%

Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure

Ahmari

Schmidt

Krane

et al. 2016

Physiological Genomics

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Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure. Physiol Genomics 48: 526 -536, 2016. First published May 27, 2016 doi:10.1152/physiolgenomics.00039.2016 is a prevalent condition with complex etiology and pathophysiology. Evidence exists of significant communication between the nervous system and the immune system (IS), and there appears to be a direct role for inflammatory bone marrow (BM) cells in the pathophysiology of hypertension. However, the molecular and neural mechanisms underlying this interaction have not been characterized. Here, we transplanted whole BM cells from the beta 1 and 2 adrenergic receptor (AdrB1 tm1Bkk AdrB2 tm1Bkk /J) knockout (KO) mice into near lethally irradiated C57BL/6J mice to generate a BM AdrB1.B2 KO chimera. This allowed us to evaluate the role of the BM beta 1 and beta 2 adrenergic receptors in mediating BM IS homeostasis and regulating blood pressure (BP) in an otherwise intact physiological setting. Fluorescence-activated cell sorting demonstrated that a decrease in systolic and mean BP in the AdrB1.B2 KO chimera is associated with a decrease in circulating inflammatory T cells, macrophage/monocytes, and neutrophils. Transcriptomics in the BM identified 7,419 differentially expressed transcripts between the C57 and AdrB1.B2 KO chimera. Pathway analysis revealed differentially expressed transcripts related to several cell processes in the BM of C57 compared with AdrB1.B2 KO chimera, including processes related to immunity (e.g., T-cell activation, T-cell recruitment, cytokine production, leukocyte migration and function), the cardiovascular system (e.g., blood vessel development, peripheral nerve blood flow), and the brain (e.g., central nervous system development, neurite development) among others. This study generates new insight into the molecular events that underlie the interaction between the sympathetic drive and IS in modulation of BP. adrenergic receptors; immune system; bone marrow; chimera; sympathetic drive DYNAMIC INTERPLAY BETWEEN the immune system (IS) and the central nervous system (CNS) exists for physiological homeostasis. The autonomic arm of the CNS, specifically the sympathetic nervous system (SNS), contributes to the diurnal function of the IS by modulating the development and release of bone marrow (BM) hematopoietic cells into circulation via the activation of beta adrenergic receptors expressed by these cells (17,18,25). Activation of the BM beta 1 and 2 adrenergic receptors, in particular, has been shown to modulate the levels of different immune cells in circulation, with inflammatory cells predominantly released during the highest activity period [i.e., night time in rodents and day time in humans (5, 9, 17, 18, 25)], an evolutionary mechanism developed to prime the system for warding off infection, should the need arise. On the other hand, the reciprocal action of an activated IS on the CNS has also been suggested, with significant evid...

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Section: Discussionmentioning

confidence: 98%

Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure

Ahmari

Schmidt

Krane

et al. 2016

Physiological Genomics

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“…111,112 The endothelium system is critical player of innate defense via releasing inflammatory cytokines and chemokines in the first barrier to recruit monocytes, neutrophils, eosinophils and basophils from the circulation. [113][114][115][116] TLR stimulation induce phenotypic and functional maturation of DC into potent antigen-presenting cells which efficiently initiate and control adaptive immune responses, while in combination with IFN-γ could induce M1 macrophage polarization that is critical for phagocytosis and killing of invading pathogens. In this section, we focus on two important cell populations in innate immunity, DCs as the key bridge between innate and adaptive immunity, and innate lymphoid cells (ILCs) as the key mediator of effector responses during innate immunity.…”

Section: Cellular Regulation Of Innate Immunity and Inflammationmentioning

confidence: 99%

Cellular and molecular regulation of innate inflammatory responses

2016

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“…Several studies demonstrated a significant increase in intracellular ROS production by peripheral blood PMNs in CP patients within a similar age range compared with sex-and age-matched healthy controls. 21,35 However, the Figure 3 Polymorphonuclear neutrophils (PMNs) of nuclear factor erythroid 2-related factor 2 (Nrf2 À/À ) mice produce low levels of catalase (CAT) and have increased migration speed. A: CAT production by bone marrow PMNs from Nrf2 À/À mice was assessed by Western blot analysis and compared with wild-type C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 99%

“…21 Erythrocytes were lysed by addition of 5 mL of Pharm Lysis buffer (BD Biosciences, Mississauga, ON, Canada). Samples were washed and cells were resuspended in phosphate-buffered saline (Sigma-Aldrich, St. Louis, MO) and quantified using a Coulter counter (Beckman Coulter, Brea, CA).…”

Section: Bone Marrow Pmn Isolationmentioning

confidence: 99%

“…21 PMN movement for bone marrow PMNs from three WT and three Nrf2 À/À mice in formylmethionineeleucyl-phenylalanine gradient was recorded using time-lapse video microscopy with differential interference contrast optics (Nikon Eclipse E1000 with Nikon Coolpix 995 camera). Images captured at 15-second intervals for 15 minutes were analyzed with ImageJ software.…”

Section: Pmn Chemotaxis Assaymentioning

confidence: 99%

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Nuclear Factor Erythroid 2-Related Factor 2 Down-Regulation in Oral Neutrophils Is Associated with Periodontal Oxidative Damage and Severe Chronic Periodontitis

Sima

Aboodi

Lakschevitz

et al. 2016

The American Journal of Pathology

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The balance between reactive oxygen species and antioxidants plays an important role in periodontal health. We previously demonstrated that high reactive oxygen species production by oral polymorphonuclear neutrophils (oPMNs) in chronic periodontitis (CP) refractory to conventional therapy is associated with severe destruction of periodontium. Herein, we show that inhibition of antioxidant production through down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in oPMN, despite enhanced recruitment in the oral cavity, is associated with severe CP. Twenty-four genes in the Nrf2-mediated oxidative stress response pathway were down-regulated in PMNs of diseased patients. Downstream of Nrf2, levels of oPMN superoxide dismutase 1 and catalase were decreased in severe CP, despite increased recruitment. Nrf2 À/À mice had more severe loss of periodontium in response to periodontitis-inducing subgingival ligatures compared with wild-types. Levels of 8-hydroxydeoxyguanosine were increased in periodontal lesions of Nrf2 À/À mice, indicating high oxidative damage. We report, for the first time, Nrf2 pathway down-regulation in oPMNs of patients with severe CP. PMNs of CP patients may be primed for low antioxidant response in the context of high recruitment in the oral cavity, resulting in increased oxidative tissue damage. (Am J Pathol 2016 http://dx

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Neutrophil transcriptional profile changes during transit from bone marrow to sites of inflammation

Cited by 50 publications

References 62 publications

Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure

Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure

Cellular and molecular regulation of innate inflammatory responses

Nuclear Factor Erythroid 2-Related Factor 2 Down-Regulation in Oral Neutrophils Is Associated with Periodontal Oxidative Damage and Severe Chronic Periodontitis

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