Neutrophils in inflammation

Savill, J.S., Wyllie, A.H., Henson, J.E., Henson, P.M. and Haslett, C. (1989a). Macrophage phagocytosis of aging neutrophils in inflammation - programmed cell death leads to its recognition by macrophages. J. Clin. Invest. 83, 865-875. 

Interleukin-8 (IL-8) is a chemokine produced by monocytes, endothelial cells, and other cells that acts as a chemotactic and activator for neutrophils and may play a role in the extravasation of neutrophils in inflammation. (For additional information, see later section on chemokines.)... 

Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson PM, Haslett C Macrophage phagocytosis of aging neutrophils in inflammation. J Clin Invest 1989 83 865-875. 

A ubiquitous phospholipid mediator (acetyl-glyceryl-ether-phosphorylcholine) in inflammation. Among others, it stimulates platelet aggregation and causes swelling, smooth contraction or dilation and neutrophil activation. 

The manifestations of inflammation with deep-seated infections such as meningitis, pneumonia, endocarditis, and urinary tract infection must be ascertained by examining tissues or fluids. For example, the presence of polymorphonuclear leukocytes (neutrophils) in spinal fluid, lung secretions (sputum), and urine is highly suggestive of bacterial infection. 

Azadniv, M. et al., Neutrophils in lung inflammation which reactive oxygen species are being measured , Inhal. Toxicol., 13, 485, 2001. 

Some of these are involved in haematopoiesis (e.g. IL-1, -3, -5, -6 GM-, M-, G-CSF) their role is described in Chapter 2. Others (e.g. IL-1, -6, -8 TNF a- GM-, M-, G-CSF) are implicated in inflammation either directly (e.g. pure IL-1 can cause some symptoms of inflammation) or indirectly, via their ability to activate immune cells that participate in the inflammatory response (e.g. lymphocytes, neutrophils and macrophages) some of these effects are described in Chapters 2 and 3. Such cytokines as IL-4, interferon-a and IL-10 may be involved in immunosuppression others, such as IL-1, IL-6, TNF a and TGF j3, are involved in tissue remodelling. 

Thus, the role of cytokines in inflammation, immune-cell function and tissue repair is varied and complex. Later sections of this book explore the cytokines generated by neutrophils during inflammatory challenge ( 7.3.4), the regulation of neutrophil function by cytokines ( 7.2.1) and human diseases associated with neutrophil dysfunction in which cytokines may play important roles ( 8.2.5, 8.8). 

Hughes, V., Humphreys, J. M., Edwards, S. W. (1987). Protein synthesis is activated in primed neutrophils a possible role in inflammation. Biosci. Rep. 7, 881-9. 

Type 3, immune complex vasculitis (serum sickness, Arthus reaction). Drug-antibody complexes precipitate on vascular walls, complement is activated, and an inflammatory reaction is triggered. Attracted neutrophils, in a futile attempt to phagocytose the complexes, liberate lysosomal enzymes that damage the vascular walls (inflammation, vasculitis). Symptoms may include fever, exanthema swelling of lymph nodes, arthritis, nephritis, and neuropathy. 

Neutrophil—Type of white blood cell involved in defense against bacteria also plays a role in inflammation. 

The cell damage associated with inflammation acts on cell membranes to cause leukocytes to release lysosomal enzymes arachidonic acid is then liberated from precursor compounds, and various eicosanoids are synthesized. As discussed in Chapter 18, the cyclooxygenase (COX) pathway of arachidonate metabolism produces prostaglandins, which have a variety of effects on blood vessels, on nerve endings, and on cells involved in inflammation. The lipoxygenase pathway of arachidonate metabolism yields leukotrienes, which have a powerful chemotactic effect on eosinophils, neutrophils, and macrophages and promote bronchoconstriction and alterations in vascular permeability. 

TheTNF-a-dependent models are mostly characterized by the apoptotic cell death of hepatocy te at the early stage of liver injury. In these models, a large number of hepatocytes undergoing apoptosis can represent a stimulus for primed neutrophils in sinusoids to transmigrate and activate, leading to hepatic inflammation and massive hepatocyte necrosis. This... 

This ligand has a lower affinity for adenosine A, and A2B receptors with pK values <6. A potent inhibitory effects on the generation of reactive oxygen species from human neutrophils and eosinophils and on the degranulation of human granulocytes subsequent to treatment with compound 30 have been described. This findings provide a useful tool for the understanding of the involvement of A2a and A3 ARs in inflammation processes. 

Inflammation is part of the first line response of the immune system to infection. Inflammation is characterized by two main components an exudative response and a cellular response. The exudative response involves the local recruitment of fluid (edema, swelling), containing proteins such as fibrin and immunoglobulins. The cellular response involves the release of cytokines from resident cells such as fibroblasts and the invasion of white blood cells into the inflamed tissue. Leukocytes take on an important role in inflammation by clearing the site from bacteria and cellular debris. In chronic inflammation an increased extravasation of neutrophils, monocytes, activated T cells, and macrophages to the inflamed site will persist. 

Lindbom, L. Regulation of vascular permeability by neutrophils in acute inflammation. Chem. Immunol. Allergy 83 146-166. 2003. 

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