The role of cytokines in the accumulation of eosinophil granulocytes in inflamed tissue has been studied extensively during recent years, and these molecules have been found to participate throughout the whole process of eosinophil recruitment. Haematopoietic cytokines such as IL‐3, IL‐5 and GM‐CSF stimulate the proliferation and differentiation of eosinophils in the bone marrow, and the release of mature eosinophils from the bone marrow into the blood is probably promoted by IL‐5. Priming of eosinophils in the blood following, for example, allergen challenge is performed mainly by IL‐3, IL‐5 and GM‐CSF. An important step in the extravasation of eosinophils is their adhesion to the vascular endothelium. Adhesion molecules are upregulated by, e.g. IL‐1, IL‐4, TNF‐α and IFN‐γ and the same cytokines may also increase the affinity of adhesion molecules both on eosinophils and endothelial cells. Finally, a number of cytokines have been shown to act as eosinophil chemotactic factors, attracting the cells to the inflammatory focus in the tissue. Some of the most important eosinophil chemoattractant cytokines are IL‐5, IL‐8, RANTES, eotaxin, eotaxin‐2, eotaxin‐3, MCP‐3, MCP‐4 and TNF‐α. Th2 cells, mast cells and epithelial cells are important sources of proinflammatory cytokines, but in recent years, the eosinophils have also been recognized as cytokine‐producing and thereby immunoregulatory cells. The aim of this paper is to review the role of cytokines in the process of eosinophil recruitment in asthma, allergy and ulcerative colitis.
Laminins (Ln) are crucial in airway morphogenesis. Because they are able to interact with inflammatory cells, they are likely to participate in inflammation accompanied by airway structural remodeling in asthma. Taking biopsies and using immunohistochemistry and quantitative image analysis, we characterized the distribution of Ln chains alpha 1, alpha 2, and beta 2 in the bronchial mucosa of patients with seasonal (n = 17), early occupational (n = 8), and chronic asthma (n = 16) for comparison with that of normal controls (n = 8). In all asthmatic patients, both Ln chains alpha 1 and beta 2 were confined to the superficial margin of the basement membrane (BM), blood vessels, and smooth muscle. The thickness of Ln beta 2 expression in BM was significantly greater in patients with chronic (1.9 +/- 0.1 microns; P < 0.001) and occupational asthma (1.7 +/- 0.1 microns; P < 0.05) than in controls (0.4 +/- 0.3 microns). Only in patients with occupational asthma was the thickness of the Ln alpha 1 layer (2.3 +/- 0.2 microns; mean +/- SEM) significantly different from that in controls (1.4 +/- 0.5 microns; P < 0.05). There was no immunoreactivity for the Ln alpha 2 chain in controls or patients with mild asthma, but in clinically severe chronic asthma we found a discontinuous staining along the epithelial margin of the BM. Since Ln chains alpha 2 and beta 2 appear to function only during morphogenesis, increased expression of these Ln chains in adult asthma patients suggests accelerated tissue turnover in the airways, possibly as a result of airway inflammation in asthma.
The high affinity Fcgamma-receptor I (FcgammaRI, CD64) is normally expressed only to a very low extent by neutrophils. During bacterial infections, however, neutrophils from adult patients significantly increase their expression of FcgammaRI. Stimulation through FcgammaRI is a highly effective way to improve various aspects of neutrophil function, including phagocytosis. In our study the expression of FcgammaRI on neutrophils from preterm (n = 9) and term (n = 3) newborn infants, children (n = 14), and adults (n = 6) during the early phase of an acute bacterial infection was investigated. Our results showed that neutrophils from newborn infants with bacterial infection expressed FcgammaRI to a significantly higher extent than both noninfected preterm (p < 0.001) and term (p < 0.001) newborn infants and that neutrophils from preterm neonates expressed FcgammaRI to the same extent as neutrophils from term neonates and older infants, children, and adults. No difference in the neutrophil cell surface expression of FcgammaRI during bacterial infections was found among newborn infants, children, and adults. Expression of FcgammaRI probably represents an important mechanism to improve neutrophil phagocytosis as well as other aspects of neutrophil function during bacterial infections, especially in preterm infants. Our study indicates that measurement of cell surface expression of FcgammaRI on neutrophils could be a useful indicator of severe bacterial infections in preterm and term neonates, as well as in older children and adults.
SUMMARYThe aim of this work was to study the expression of b 1 -and b 2 -integrins, CR1, CD44 and Fcg receptors on peripheral blood monocytes in RA. The expression of these receptors was measured by flow cytometry, before and after treatment with low-dose prednisolone. Expression of the same receptors was also measured before and after treatment with metyrapone, a substance that inhibits the synthesis of cortisol in the adrenals. The expression of the b 2 -integrins CD11a, CD11b and CD18, of CD35 (CR1), and of FcgRII and FcgRI (CD32 and CD64) on monocytes was elevated in the RA patients compared with healthy controls, while the expression of the b 1 -integrins (CD29, CD49d, CD49f) was unaffected. A significant correlation between monocyte expression of CD64 and C-reactive protein (CRP), and blood platelet count, respectively, was found in the group of patients with RA. After 4-6 weeks of treatment with low-dose prednisolone, the expression on the monocytes of CD11a, CD11b, CD18, CD35, CD32 and CD64 was normalized. A significant correlation (r ¼ 0·64, P ¼ 0·02) was found between the decrease in expression of CD11b and clinical improvement after prednisolone treatment. Two days of metyrapone treatment, which significantly lowered the serum cortisol levels, elevated the expression of CD35 and CD49f. Priming of peripheral monocytes seems to be one of the mechanisms behind the recruitment of monocytes to the rheumatoid synovium. One reason for the good clinical effects of prednisolone in RA could be a down-regulation of adhesion and phagocytosis receptors on monocytes.
The increased serum levels of lysozyme and MPO, but not of HNL and lactoferrin in RA could indicate a stimulated secretory activity of mononuclear phagocytes. The measurement of serum lysozyme, as an indicator of monocyte/macrophage activity, might be used to study disease activity in RA.
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