Nathan, C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6: 173-182

Department of Microbiology and Immunology, Weill Cornell Medical College, Weill Graduate School of Medical Sciences of Cornell University, Box 57, 1300 York Avenue, New York 10021, USA.
Nature reviews. Immunology (Impact Factor: 34.99). 04/2006; 6(3):173-82. DOI: 10.1038/nri1785
Source: PubMed


Scientists who study neutrophils often have backgrounds in cell biology, biochemistry, haematology, rheumatology or infectious disease. Paradoxically, immunologists seem to have a harder time incorporating these host-defence cells into the framework of their discipline. The recent literature discussed here indicates that it is appropriate for immunologists to take as much interest in neutrophils as in their lymphohaematopoietic cousins with smooth nuclei. Neutrophils inform and shape immune responses, contribute to the repair of tissue as well as its breakdown, use killing mechanisms that enrich our concepts of specificity, and offer exciting opportunities for the treatment of neoplastic, autoinflammatory and autoimmune disorders.

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    • "Neutrophils represent the first line of defense against invading pathogens and also play crucial roles in the pathogenesis of non-infectious diseases like acute lung injury (ALI) 1 and transfusion-related acute lung injury (TRALI) [1] [2] [3] [4]. While induction of the neutrophil antimicrobial arsenal is a physiological response to infection, its aberrant mobilization is thought to be causative for lung tissue damage occurring during ALI and TRALI [2] [5]. "
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    ABSTRACT: Background: Global analysis of stimulus-dependent changes in the neutrophil phosphoproteome will improve the understanding of neutrophil signal transduction and function in diverse disease settings. However, gel-free phosphoproteomics of neutrophils in clinical studies is hampered by limited sample amounts and requires protein extract stability, efficient tryptic digestion and sensitive phosphopeptide enrichment in a protease-rich environment. For development of an appropriate workflow, we assessed neutrophil protein stability in urea-based lysis buffers and determined feasibility of gel-free phosphoproteomic analyses using polymer-based metal ion affinity capture (PolyMAC). Methods: Western blotting, phosphopeptide enrichment and mass spectrometric analyses of samples of neutrophils were performed. Results: Degradation of proteins in neutrophil extracts was observed after preparation with an urea-containing lysis buffer and could be prevented by addition of highly concentrated protease inhibitors. Subsequent tryptic digestion and PolyMAC-based phosphopeptide enrichment proved efficient with accordingly prepared neutrophil samples. Applying the new workflow, formyl-methionyl-leucyl-phenylalanine-induced phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) was detected after gel-free and gel-based phosphoproteomic analyses as proof of principle from 20 ml of whole blood. Furthermore, phosphorylation of other ERK1/2 pathway-associated proteins was monitored. Conclusion: We provide a workflow for efficient, gel-free phosphoproteome analyses with small-sized neutrophil samples, suitable for application in clinical studies.
    Clinica chimica acta; international journal of clinical chemistry 10/2015; 451(Pt B). DOI:10.1016/j.cca.2015.09.030 · 2.82 Impact Factor
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    • "Inflammatory disorders are due to excessive production of pro-inflammatory mediators, such as tumor necrosis factor (TNF)α, granulocyte-macrophage colonystimulating factor (GM-CSF), interleukin (IL)-1, IL-6, IL-8, leukotriene B4 and platelet-activating factor (PAF), to the activity of inflammatory cells such as neutrophils, monocytes and macrophages, and to the excessive production of reactive oxygen species (ROS) (Ley, 2002; Nathan, 2006). Polymorphonuclear neutrophils play a key role in host defenses against invading microorganisms (Hampton et al., 1998), but excessive neutrophil activation participates in tissue damage associated with inflammatory disorders (Babior, 2000). "
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    ABSTRACT: Citrillus colocynthis peel aqueous extract (CCPAE) is widely used to treat disorders such as inflammation, ulcers and infections, but its pharmacological target is not known. The objectives of this work were to study the effect of C. colocynthis peel aqueous extract, on human neutrophil reactive oxygen species (ROS) production in vitro, and to evaluate its protective effect on lipopolysaccharide (LPS)-induced lung inflammation in vivo in mice. Neutrophils were isolated from blood of healthy volunteers. ROS generation was measured by luminol-amplified chemiluminescence. Superoxide anion generation was detected by the cytochrome c reduction assay. H 2 O 2 was detected by horseradish peroxidase (HRP)-amplified chemiluminescence assay. Myeloperoxidase (MPO) activity was measured by the tetramethylbenzidine oxidation method. Lung inflammation was induced in mice by LPS instillation. CCPAE inhibited luminol-amplified chemiluminescence of resting neutrophils and N-formyl-methionyl-leucyl-phenylalanine (fMLF)-or phorbolmyristate acetate (PMA)-stimulated neutrophils, in a concentration-dependent manner. CCPAE also inhibited superoxide anion generation; and did not scavenge H 2 O 2 and superoxide anions nor inhibited MPO activity in vitro suggesting that it inhibits nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. In vivo studies showed that CCPAE attenuated LPS-induced lung inflammation in mice. This study shows that CCPAE inhibits neutrophil ROS production and attenuates LPS-induced lung inflammation in mice. Inhibition of NADPH oxidase activation by CCPAE could explain its anti-inflammatory action.
    • "e l s e v i e r . c o m / l o c a t e / b b a m c r responses [23] [24]. There is a recent discussion on the possible existence of different subsets of neutrophils [26] as well as a new emphasis on differences between neutrophils in various functional compartments [28]. "
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    ABSTRACT: Mechanotransduction refers to the processes through which cells sense mechanical stimuli by converting them to biochemical signals and, thus, eliciting specific cellular responses. Cells sense mechanical stimuli from their 3D environment, including the extracellular matrix, neighboring cells and other mechanical forces. Incidentally, the emerging concept of mechanical homeostasis, long term or chronic regulation of mechanical properties, seems to apply to neutrophils in a peculiar manner, owing to neutrophils' ability to dynamically switch between the activated/primed and deactivated/deprimed states. While neutrophil activation has been known for over a century, its deactivation is a relatively recent discovery. Even more intriguing is the reversibility of neutrophil activation and deactivation. We review and critically evaluate recent findings that suggest physiological roles for neutrophil activation and deactivation and discuss possible mechanisms by which mechanical stimuli can drive the oscillation of neutrophils between the activated and resting states. We highlight several molecules that have been identified in neutrophil mechanotransduction, including cell adhesion and transmembrane receptors, cytoskeletal and ion channel molecules. The physiological and pathophysiological implications of such mechanically induced signal transduction in neutrophils are highlighted as a basis for future work. Copyright © 2015. Published by Elsevier B.V.
    Biochimica et Biophysica Acta 07/2015; 1853(11). DOI:10.1016/j.bbamcr.2015.07.015 · 4.66 Impact Factor
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