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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    • "Early neutrophil accumulation triggers monocyte migration and inflammation (Savill et al, 1989 ), and diminished neutrophil accumulation can ameliorate NAFLD (Nathan, 2006). To clarify whether defective neutrophil migration contributes to the milder hepatic steatosis in MCD-diet p38c/d Lyzs-KO mice, we depleted neutrophils in MCD-diet Lyzs-Cre mice by administering anti-Ly6G antibody. "
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a major health problem and the main cause of liver disease in Western countries. Although NAFLD is strongly associated with obesity and insulin resistance, its pathogenesis remains poorly understood. The disease begins with an excessive accumulation of triglycerides in the liver, which stimulates an inflammatory response. Alternative p38 mitogen-activated kinases (p38γ and p38δ) have been shown to contribute to inflammation in different diseases. Here we demonstrate that p38δ is elevated in livers of obese patients with NAFLD and that mice lacking p38γ/δ in myeloid cells are resistant to diet-induced fatty liver, hepatic triglyceride accumulation and glucose intolerance. This protective effect is due to defective migration of p38γ/δ-deficient neutrophils to the damaged liver. We further show that neutrophil infiltration in wild-type mice contributes to steatosis development by means of inflammation and liver metabolic changes. Therefore, p38γ and p38δ in myeloid cells provide a potential target for NAFLD therapy.
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    • "During inflammation neutrophils are rapidly recruited to the infected or injured tissue. However, due to the potential tissue-damaging effects of PMN, their finetuned regulation at the inflammatory site is required[53]. Indeed, exacerbated or overshooting inflammatory response with high neutrophil influx may account for chronic inflammatory diseases[5]. "
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    • "Activation of neutrophils with microbial or inflammatory stimuli results in the release of neutrophil extracellular traps (NETs)[4]. NETs are extracellular web-like structures consisting of cfDNA with histones, granules, and cytoplasmic proteins, including neutrophil elastase (NE), myeloperoxidase, cathepsin G, proteinase 3, gelatinase, LL-37, lactoferrin, and calprotectin[26,27]. These structures bind to microorganisms , prevent them from spreading, and ensure a high local concentration of neutrophil granule enzymes to kill bacteria and fungi[4]. "
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