Diseases neutrophils implicated

However, it is now recognised that neutrophils can contribute to host-tissue damage if they are activated to secrete reactive oxidants and granule enzymes, and if the local concentrations of anti-oxidants and protease inhibitors within the tissue are low or defective. Thus, inappropriate neutrophil activation leading to host-tissue damage has been implicated in reperfusion injury, Crohn s disease, adult respiratory distress syndrome (ARDS) and rheumatoid arthritis. In these conditions, it is envisaged that neutrophils accumulate in tissues and become inappropriately activated to secrete their cytotoxic products, which then initiate or contribute to host-tissue damage. 

Human neutrophil elastase (HNE) is a serine containing enzyme which is one of the most destructive of proteolytic enzymes, being able to catalyze the hydrolysis of the components of connective tissue. It has been implicated in the development of diseases such as emphysema, cystic fibrosis, and rheumatoid arthrisis. /3-Sultams are excellent candidates for exploring the mechanism of sulfonation and possible inhibition of serine protease enzymes. A-Benzoyl... 

Due to its broad specificity and high concentrations within neutrophils NE has been implicated in the development and progression of several lung diseases such as pulmonary emphysema, cystic fibrosis, adult respiratory distress... 

Neutrophil elastase is implicated in the induction of bronchial disease, causing structural changes in lungs, impairment of mucociliary clearance, and impairment of host defenses. Protease inhibitors, namely, inhibitors of neutrophil elastase, are being investigated currently for the treatment of COPD. 

Due to its broad specificity and high concentrations within neutrophils. NE has been implicated in the development and progression of several lung diseases such as pulmonary emphysema, cystic fibrosis, adult respiratory distress syndrome, and chronic bronchitis [2-4]. During phagocytosis and neutrophil turnover, there is a release of elastase into the extracellular environment which, if not controlled, can result in extensive damage to connective tissue. The destructive effect of elastase is normally controlled by endogenous proteinase inhibitors... 

BALB/c animals display IL-12 p40 mRNA, in apparent contrast to PMN from the genetically susceptible C57BL/6 mouse strain [73]. Neutrophil depletion of BALB/c mice exacerbates infection. This is accompanied by decreased Thl cytokines (IL-12 p40, IFN-7, TNF-a) and increases in the IL-10 response in spleens of infected animals, suggesting a Thl to Th2 switch [73]. In contrast, during T. cruzi infection of susceptible C57BL/6 mice, neutrophil depletion induces resistance to disease and enhances Thl cytokine production. Neutrophils have also been implicated in induction of the CD4-I- Th2 response in L. major-infected BALB/c mice [85]. Thus, the early burst of IL-4 that instructs Th2 differentiation in this model is prevented by neutrophil depletion, and draining lymph node T cells remain IL-12-responsive, unlike cells from nondepleted mice. 

Chemokines regulate the migration of cells in vivo and dysregulated expression of chemokines and their receptors are implicated in autoimmune and inflammatory diseases. Inflammatory arthritides, such as rheumatoid arthritis (RA), are characterized by the recruitment of inflammatory cells into joints. The K/BxN serum transfer mouse model of inflammatory arthritis shares many similar features with RA. In this autoantibody-induced model of arthritis, neutrophils are the critical immune cells necessary for the development of joint inflammation and damage. In this review, we describe the use of several methods to study the role of chemoattractant receptors, including chemokine receptors, on the recruitment of neutrophils into the joint in the K/BxN model of inflammatory arthritis. This includes both traditional methods, such as flow cytometry, immunohistochemistry, and enzyme assays, as well as multiphoton in vivo microscopy that we have adapted to study the role of immune cell trafficking in and around the joint in live mice. 

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