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- Erjefält, Jonas, et al.
(författare)
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Acute allergic responses induce a prompt luminal entry of airway tissue eosinophils.
- 2003
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Ingår i: American Journal of Respiratory Cell and Molecular Biology. - 1535-4989. ; 29:4, s. 439-448
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Tidskriftsartikel (refereegranskat)abstract
- Traditionally, traffic and activation of eosinophils in asthmatic airways are thought to take place during the late-phase allergic reaction. The present study tests the hypothesis that when eosinophils are present in the tissue before allergen exposure, as in chronically inflamed asthmatic airways, acute anaphylactic reactions initiate an eosinophil response. Using a guinea-pig allergic model, where eosinophilia is present at baseline conditions, the traffic of resident eosinophils was examined in vivo immediately after allergen challenge. By 2 min after challenge, eosinophils had moved up to apical epithelial positions. Within 10 min, a marked migration of eosinophils into the airway lumen was demonstrated. Along with the allergen-induced egression of eosinophils, acute luminal entry of plasma proteins and eotaxin occurred. Eosinophil egression was effectively inhibited by the antiexudative drug formoterol, whereas the proexudative drug bradykinin could in naive animals evoke a prompt luminal entry of eosinophils. In conclusion, the present study demonstrates that acute allergic reactions initiate a prompt transepithelial migration of resident eosinophils. Our data further suggest that this response in part is initiated by the plasma exudation response, which may alter the transepithelial gradient of eosinophil chemoattractants including eotaxin. We propose that prompt eosinophil response is a significant component of the acute phase of allergic reactions when occurring in airways where these cells are already present in the mucosa.
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| 2. |
- Erjefält, Jonas, et al.
(författare)
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Rapid and efficient clearance of airway tissue granulocytes through transepithelial migration.
- 2004
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Ingår i: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 59:2, s. 136-143
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clearance of tissue granulocytes is central to the resolution of airway inflammation. To date the focus has been on apoptotic mechanisms of cell removal and little attention has been given to alternative processes. The present study explores transepithelial migration as a mechanism of cell clearance. Method: Guinea pig tracheobronchial airways where eosinophils are constitutively present in the mucosal tissue were studied. A complex topical stimulus (allergen challenge) was applied and the fate of the eosinophils was determined by selective tracheobronchial lavage and histological examination of the tissue. Results: Within 10 minutes of the allergen challenge, massive migration of eosinophils into the airway lumen occurred together with a reduction in tissue eosinophil numbers. Cell clearance into the lumen continued at high speed and by 30 and 60 minutes the tissue eosinophilia had been reduced by 63% and 73%, respectively. The marked transepithelial migration (estimated maximal speed 35 000 cells/min x cm2 mucosal surface) took place ubiquitously between epithelial cells without affecting epithelial integrity as assessed by transmission and scanning electron microscopy. Eosinophil apoptosis was not detected but occasional cytolytic eosinophils occurred. Conclusion: This study shows that luminal entry has a remarkably high capacity as a granulocyte elimination process. The data also suggest that an appropriate stimulus of transepithelial migration may be used therapeutically to increase the resolution of inflammatory conditions of airway tissues.
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| 3. |
- Malm-Erjefält, Monika, et al.
(författare)
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Degranulation status of airway tissue eosinophils in mouse models of allergic airway inflammation
- 2001
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Ingår i: American Journal of Respiratory Cell and Molecular Biology. - 1535-4989. ; 24:3, s. 352-359
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophil degranulation is a characteristic feature of asthma and allergic rhinitis. However, degranulated eosinophils have not been convincingly demonstrated in the common mouse models of these airway diseases. This study uses eosinophil peroxidase (EPO) histochemistry and transmission electron microscopy (TEM) analysis to assess eosinophil degranulation in the airways of ovalbumin (OVA)-sensitized and challenged BALB/c and C57BL/6 mice. Using TEM we also examined mouse and human blood eosinophils after in vitro incubation with formyl-Met-Leu-Phe (fMLP) or phorbol myristate acetate (PMA). Although OVA exposure induced significant nasal and lung eosinophilia, we did not observe any of the known cellular processes by which eosinophils release their granule products, i.e., eosinophil cytolysis, piecemeal degranulation, and exocytosis. The occurrence of other allergen-induced degranulation events was ruled out because no difference in granule morphology was observed between lung-tissue eosinophils and blood or bone-marrow eosinophils from control animals. Accordingly, there was no detectable extracellular EPO in lung tissues of allergic mice. Similarly, mouse blood eosinophils remained nondegranulated in vitro in the presence of fMLP and PMA, whereas the same treatment of human eosinophils resulted in extensive degranulation. This investigation indicates that OVA-induced airway inflammation in the present mouse strains does not involve significant eosinophil degranulation. It is speculated that this dissimilarity from the human disease may be due to a fundamental difference in the regulation of mouse and human eosinophils.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Erjefält, Jonas, et al.
(författare)
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Degranulation patterns of eosinophil granulocytes as determinants of eosinophil driven disease
- 2001
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Ingår i: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 56:5, s. 341-344
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Degranulation of eosinophils in target tissues is considered a key pathogenic event in major chronic eosinophilic diseases. However, because of a lack of appropriate methods, little is known about degranulation of eosinophils in common eosinophilic diseases. METHODS: Using transmission electron microscopic (TEM) analysis, a novel approach has been devised and validated to quantify eosinophil degranulation in human tissues (assessed in individual cells as percentage granules with structural signs of protein release). Biopsy specimens from patients with inflammatory bowel disease, allergic rhinitis, asthma, and nasal polyposis were evaluated. RESULTS: All conditions displayed a similar degree of local tissue eosinophilia, with no differences being observed in eosinophil numbers in the airway mucosa of patients with airway diseases and the colonic mucosa of those with inflammatory bowel disease (IBD). In contrast, marked differences in the mean (SE) extent of eosinophil degranulation were observed between the patient groups; IBD 9.3 (1.4)% altered granules, artificial and natural allergen challenge induced allergic rhinitis 67.8 (6.8)% and 86.6 (3.0)%, respectively, asthma 18.1 (2)%, and nasal polyposis 46.6 (7.6)%. CONCLUSIONS: This study provides the first quantitative data which show that different eosinophilic conditions, despite having similar numbers of tissue eosinophils, may exhibit markedly different degranulation patterns. The present assessment of piecemeal degranulation would thus make it possible to delineate the conditions under which eosinophils are likely to contribute to disease processes. This novel type of analysis may also guide and validate anti-eosinophilic treatment options.
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| 10. |
- Greiff, Lennart, et al.
(författare)
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Loss of size-selectivity at histamine-induced exudation of plasma proteins in atopic nasal airways.
- 2002
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 22:1, s. 28-31
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Tidskriftsartikel (refereegranskat)abstract
- Plasma proteins occur in the airway lumen in inflammatory airway diseases. This study tests the hypothesis that airway microvascular-epithelial exudation of plasma proteins, as induced by a non-injurious inflammatory mediator, is characterized by loss of size-selectivity. Using a nasal pool-device, the nasal mucosa of 10 allergic individuals, without current disease, was sequentially exposed to saline and histamine (40 and 400 microg ml(-1)). Nasal lavage fluid and blood-levels of albumin (69 kD) and alpha2-macroglobulin (720 kD) were determined. Histamine produced concentration-dependent exudation of albumin and alpha2-macroglobulin. The albumin/alpha2-macroglobulin concentration ratio of the saline lavage fluid (baseline) was 40+/-19. However, at the histamine challenges the ratios were 25+/-3 and 22+/-2, respectively, which did not differ from that of circulating plasma (22+/-2). We conclude that there is minor and size-selective luminal entry of plasma proteins at baseline. However, at concentration-dependent exudative responses to histamine, plasma proteins enter the airway lumen without being sieved. These data indicate that inflammatory stimulus-induced extravasation, lamina propria distribution and paracellular epithelial passage of plasma occur with minimal size-selectivity. Inferentially, the full immunological capacity of plasma proteins may readily be made available at the surface of human intact airway mucosa.
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