Numbers of eosinophiles

An increased number of polymorphonuclear granulocytes in sputum often suggests continual bronchial irritation, whereas an increased number of eosinophils may suggest an allergic component. The most common bacterial isolates (expressed in percentages of total cultures) identified from sputum culture in patients experiencing an acute exacerbation of chronic bronchitis are as follows ... 

A3 receptors are present on human eosinophils and couple to signalling pathways that lead to cell activation ( Kohno et al. 1996a Reeves et al. 2000). Despite this it has not proven easy to demonstrate the functional consequences of activation of these sites (Reeves et al. 2000). Nevertheless, the chronic inflammation in asthma is characterised by extensive infiltration of the airways by activated eosinophils (Holgate 1999 Pearlman 1999) and it remains possible that the elevated adenosine concentrations associated with asthma would contribute to eosinophil activation through stimulation of A3 receptors. In addition, it has been speculated that activation of A3 receptors may protect eosinophils from apoptosis (Gao et al. 2001). Thus, blockade of A3 receptors may reduce the numbers of eosinophils and their activation thereby reducing the pro-inflammatory burden in the lung. Consistent with this, following 6 weeks treatment of mild asthmatics with theophylline there was a... 

IL-5 is usually not present in high levels in humans. However, in a number of disease states where the number of eosinophils is elevated, high levels of IL-5 and its mRNA can be found in the circulation, tissue and bone marrow. These conditions include the diseases of the respiratory tract, hematopoietic system, gut and skin. Some other examples include food and drug allergies, atopic dermatitis, aspirin sensitivity and allergic or nonallergic respiratory diseases. 

Not all classes of leukocytes are affected by glucocorticoids in the same way. The total leukocyte count is increased, but the number of eosinophilic leukocytes falls, as does the lymphocyte count. The number of monocytes is reduced, as is their capacity to perform phagocytosis. 

Hypersensitivity reactions can occur with statins (SEDA-13, 1328 3), and an otherwise unexplained case of interstitial lung disease and pleural effusion developed during treatment with simvastatin for 6 months the number of eosinophils in the bronchoalveolar lavage fluid normalized a few days after withdrawal (4). 

Due to the low number of eosinophils in peripheral blood, especially in guinea pigs, eosinophils are elicited in the peritoneal cavity by repeated injection of horse serum. Eosinophils are then purified to >95% by use of a discontinous Percoll gradient. The yield of eosinophils varies but we usually use 1 exbreeder donor for every 2 4 recipients. 

This method of measuring eosinophil accumulation in vivo has the advantage that it does not require the use of radioactive material. However, it is less sensitive to low doses of chemoattractant, although this can be overcome by the intravenous injection of IL-5 to boost the numbers of eosinophils in the circulation (7). The isolation of eosinophils, for use as a standard, and the preparations for intradermal injections have been described in Subheadings... 

A biopsy is often required to make a diagnosis of most types of liver disease. A specimen of liver can be used to identify fibrosis, cirrhosis, cholestasis and hepatitis, both acute and chronic, and tumours. Biochemical measurements can also be taken from a biopsy specimen to determine iron and copper content, virology, microbiology and haematology (e.g. increased numbers of eosinophils in a drug-induced cause). The biopsy can give an indication of the extent of the liver damage. See Chapter 3 for slides of liver biopsies. 

In animal studies, rats exposed to dusts of ammonium diuranate containing 6.8 mg U/m for 6 hours a day, 5 days per week for 30 days developed a rise in neutrophils, a decrease in lymphocytes, a moderate fall in the white blood cell count, and a rise in the number of eosinophils (Dygert 1949b). Rats exposed to airborne uranyl nitrate hexahydrate containing 9.5 mg U/m 8 hours a day, 5 days a week for... 

The bronchial histopathology of patients who have died of asthma shows an intense infiltration of the bronchial mucosa with inflammatory ceUs, particularly eosinophils, macrophages, lymphocytes and to a lesser extent neutrophils. Deposition of eosinophil products in the bronchial epithelium and subepithelium is a particularly prominent feature (Filley etal., 1982). Epithelial denudation, dilatation of blood vessels, mucosal oedema and hypertrophy of both submucosal glands and bronchial smooth muscle are other features. Many of these features of asthma deaths are also observed in milder and well-controlled asthmatics. Elevated numbers of eosinophils, moncytes/macrophages and activated lymphocytes are persistent features observed in bronchial biopsies... 

Pathologic studies have demonstrated a perivascular, lymphocytic infiltrate with eosinophils in the dermis, fascia, and skeletal muscle, with variable numbers of eosinophils. The perivascular infiltrate was accompanied by thickening of the capillary and arteriolar endothelium in dermal, fascial, and muscle vessels. The frequent occurrence of microangiopathy (disease of the small blood vessels) in biopsy specimens suggests that ischemia (deficiency of blood supply) may contribute to tissue injury. Deposition of major basic protein (an eosinophil-specific protein) in affected tissue of some patients suggests that cytotoxic eosinophil degranulation products may also play a role in the pathogenesis of EMS. 

Inhibition of the normal immune response results from a gradual destruction of lymphoid tissue, followed by a decline in antibody production and a decrease in the numbers of eosinophils, basophils, and lymphocytes. The reduction in T-lymphocyte counts by glucocorticoids can occur acutely as a result of the redistribution of these cells from the intravascular space to the spleen, lymph nodes, and bone marrow. Thus an increase in the neutrophil count is commonly observed after glucocorticoid administration. The major suppressive effects of glucocorticoids on the inflamniatory response and the immune system appear to be through the modulation of cytokine production via an inhibition of nuclear factor kappa B (NF-kB) expression and nuclear translocation. Cytoldnes released from immunocompetent cells mediate both the acute and chronic phases of inflammation and participate in the control of the immune response (see Chapter 22). 

Vinke et al. [252(111)] demonstrated cellular changes in the nasal mucosa of tobacco-smoke-exposed non-atopic children, i.e. children not having the atopic constitution. They found a cellular infiltrate in the nasal mucosa of ETS-exposed children similar to that found in the nasal mucosa of allergic children, including an increased number of eosinophils and IgE-positive cells. 

As far as the prediction of asthma is concerned, eosinophils as well as their mediators (e.g. eosinophil cationic protein, peroxidase and protein X) have been studied in infancy in order to identify individuals who are developing chronic disease. In a Norwegian study cohort, wheezing infants had significantly higher levels of serum eosinophil cationic protein compared to controls [18(11)]. Whether concentrations of mediators from eosinophils also predict the chronic disease process remains to be shown. Studies of eosinophils in bronchial biopsies have suggested that increased numbers of eosinophils are risk factors for chronic asthma [19(11)]. So far, none of the various immunological markers has been found suitable for the prediction of atopy or asthma on an individual level. 

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