| 1. |
- 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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Association between inflammation and epithelial damage-restitution processes in allergic airways in vivo
- 1997
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 27:11, s. 1344-1355
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between allergen challenge-induced sites of epithelial damage and the distribution of leucocytes and extravasated plasma remain unexplored. OBJECTIVE: To study neutrophils, eosinophils, and fibrinogen at allergen challenge-induced patchy epithelial damage-restitution sites in guinea-pig trachea. METHODS: After local challenge tracheal tissue (cryo sections and whole-mounts) and lumen (selective tracheal lavage) were examined at 1, 5, and 24 h. Eosinophils, neutrophils and fibrinogen were identified by histochemistry. RESULTS: Neutrophils increased markedly in tracheal lavage fluids and in tissue and were strongly associated with the challenge-induced epithelial craters of damage-restitution. At 1 and 24 h eosinophils were increased in the tracheal lumen whereas the surrounding tissue displayed a reversed pattern. Gels rich in fibrinogen, neutrophils, and eosinophils were present in epithelial crater areas, protruding into the lumen. Clusters of free eosinophil granules, Cfegs, released through lysis of eosinophils, and neutrophils with long cytoplasmatic protrusions abounded in these crater areas. CONCLUSION: The present findings provide important new insights into allergic airways where sites of epithelial damage-restitution processes emerge as the major loci for eosinophil, neutrophil, and plasma protein activities, the latter likely causing leukocyte adhesion and activation in vivo. The distribution of eosinophils in this study suggests roles of these cells both in airway mucosa and in regional lymph nodes. Based on the present study we also propose that lysis of eosinophils and Cfegs generation are a major paradigm for activation of these cells in vivo.
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| 3. |
- Erjefält, Jonas, et al.
(författare)
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Prompt epithelial damage and restitution processes in allergen challenged guinea-pig trachea in vivo
- 1997
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 27:12, s. 1458-1470
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about the induction and the morphology of epithelial damage, and of the ensuing epithelial restitution processes in allergic airways. OBJECTIVE: To examine epithelial damage and restitution in allergen challenged guinea-pig trachea. METHODS: Whole-mount techniques, transmission and scanning electron microscopy, cryosectioning, and histochemical staining were used. Cell proliferation was monitored by BrdU-immunohistochemistry. RESULTS: Allergen challenge produced patchy, crater-like, and leucocyte-rich epithelial damage sites. At 1, 5, and 24 h damage was associated with poorly differentiated epithelial restitution cells. Already at 1 h the epithelial craters had a floor of flattened restitution cells and the damaged areas comprised < 1% of the mucosal surface area (whole-mount preparations). In contrast, cryo sections displayed large areas (approximately 20%, 1 h) of denudation. Epithelial, and subepithelial (fibroblasts, smooth muscle) proliferation was increased 5 and 24 h after challenge (P < 0.01). CONCLUSION: Within 1 h allergen challenge has induced patchy damage sites where epithelial restitution is already advanced; although easily produced by cryosectioning frank denudation was not evident in whole-mount preparations. The present findings may explain the well maintained, functional tightness of allergic airways displaying epithelial damage, shedding, and even denudation. The present data also suggest the possibility that epithelial damage-restitution may be causative to allergic airway remodelling.
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| 4. |
- Korsgren, Magnus, et al.
(författare)
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Allergic eosinophil-rich inflammation develops in lungs and airways of B cell-deficient mice
- 1997
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Ingår i: Journal of Experimental Medicine. - 1540-9538. ; 185:5, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulins (Ig), particularly IgE, are believed to be crucially involved in the pathogenesis of asthma and, equally, in allergic models of the disease. To validate this paradigm we examined homozygous mutant C57BL/6 mice, which are B cell deficient, lacking all Ig. Mice were immunized intraperitoneally with 10 micrograms ovalbumin (OVA) plus alum, followed by daily (day 14-20) 30 min exposures to OVA aerosol (OVA/OVA group). Three control groups were run: OVA intraperitoneally plus saline (SAL) aerosol (OVA/SAL group); saline intraperitoneally plus saline aerosol; saline intraperitoneally plus OVA aerosol (n = 6-7). Lung and large airway tissues obtained 24 h after the last OVA or SAL exposure were examined by light microscopy and transmission electron microscopy (TEM). The Ig-deficient mice receiving OVA/ OVA treatment had swollen and discolored lungs and exhibited marked eosinophilia both in large airway subepithelial tissue (49.2 +/- 12.0 cells/mm basement membrane [BM] versus OVA/ SAL control 1.2 +/- 0.3 cells/mm BM; P < 0.001), and perivascularly and peribronchially in the lung (49.3 +/- 9.0 cells/unit area versus OVA/SAL control 2.6 +/- 0.6 cells/unit area; P < 0.001). The eosinophilia extended to the regional lymph nodes. TEM confirmed the subepithelial and perivascular localization of eosinophils. Mucus cells in large airway epithelium increased from 1.5 +/- 0.8 (OVA/SAL mice) to 39.5 +/- 5.7 cells/mm BM in OVA/OVA treated mice (P < 0.001). OVA/SAL mice never differed from the other control groups. Corresponding experiments in wild-type mice (n = 6-7 in each group) showed qualitatively similar but less pronounced eosinophil and mucus cell changes. Macrophages and CD4+ T cells increased in lungs of all OVA/OVA-treated mice. Mast cell number did not differ but degranulation was detected only in OVA/OVA-treated wild-type mice. Immunization to OVA followed by OVA challenges thus cause eosinophil-rich inflammation in airways and lungs of mice without involvement of B cells and Ig.
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| 5. |
- Korsgren, Magnus, et al.
(författare)
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Lack of systemic anaphylaxis and aeroallergen-induced airway plasma extravasation in allergic immunoglobulin-deficient mice
- 1999
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 118:1, s. 67-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Ig-deficient mice allergen challenge-induced pulmonary late phase inflammation is at least as pronounced as in wild-type animals. This study investigates immediate hypersensitivity responses in these mice. METHODS: To examine the acute plasma extravasation response in airway tissue, immunized Ig-deficient and wild-type mice and sham-immunized wild-type controls were subjected to 15 min ovalbumin aerosol challenge. 125I-albumin was injected (i.v.) 1 min prior to challenge. Immediately after challenge 131I-albumin was injected and the experiment was terminated. Plasma and trachea were analyzed for 125I and 131I, and the amount of extravasated plasma in the trachea was calculated. To study the development of systemic anaphylaxis immunized Ig-deficient and wild-type animals received intravenous allergen challenge followed by determination of mast cell responses and plasma histamine levels. RESULTS: Allergen aerosol-exposed immunized wild-type mice exhibited marked plasma extravasation in the trachea (pd0.01 vs. wild-type controls), but in the corresponding Ig-deficient mice there was no increased extravasation. Immunized Ig-deficient mice receiving intravenous allergen challenge were resistant to anaphylactic shock. By contrast, the wild-type animals developed systemic anaphylaxis, accompanied by plasma extravasation, mast cell degranulation, elevated plasma histamine and rapid death. CONCLUSION: The present data are evidence that immunoglobulins are crucial for the development of immediate (type 1) responses. These findings together with our previous observations on late-phase pulmonary responses suggest that immediate hypersensitivity processes are unimportant for development of the late phase inflammation in the respiratory tract of mice.
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| 6. |
- Mei, Qi, et al.
(författare)
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Eosinophil infiltration and activation at the gastric ulcer margin in rats.
- 2002
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Ingår i: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 14:5, s. 503-511
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND : Recruitment and activation of eosinophils have been studied intensely in asthma and other allergic diseases. Less is known about the infiltration and behaviour of eosinophils during gastric ulcer healing. AIM : To examine the tissue infiltration and activation of eosinophils in the ulcer margin at different time points after ulcer induction (days 1-15). METHODS : Eosinophil peroxidase (EPO) staining and transmission electron microscopy (TEM) were used to observe eosinophil infiltration and activation in rats with acetic-acid-induced ulcer in the oxyntic mucosa. The distribution of macrophages was evaluated by immunocytochemistry using the macrophage-specific antibodies ED1 and ED2. RESULTS : There was a prominent increase in eosinophils around the ulcer margin at day 1 after ulcer induction, which peaked at day 5. TEM revealed characteristic signs of eosinophil activation, including cytolysis and piecemeal degranulation. Eosinophil cytolysis was the major form of activation, seen most frequently at day 5. A few scattered apoptotic eosinophils could also be observed. In normal controls and sham-operated rats, activated eosinophils were detected rarely. The distribution pattern of infiltrated eosinophils closely resembled that of macrophages at the ulcer margin. However, in the central part of the granulation tissue (at day 5) only macrophages could be found. CONCLUSIONS : There is marked infiltration and signs of activation of eosinophils together with macrophages at the margin of newly formed ulcers.
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| 7. |
- Persson, Carl, et al.
(författare)
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Contribution of plasma-derived molecules to mucosal immune defence, disease and repair in the airways
- 1998
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 47:4, s. 302-313
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Forskningsöversikt (refereegranskat)abstract
- This review discusses recent observations, in health and disease, on the release and distribution of plasma-derived molecules in the airway mucosa. Briefly, the new data on airway mucosal exudation mechanisms suggest that the protein systems of plasma contribute significantly to the mucosal biology, not only in injured airways but also in such mildly inflamed airways that lack oedema and exhibit no sign of epithelial derangement. Plasma as a source of pluripotent growth factor, adhesive, leucocyte-activating, etc., molecules may deserve a prominent position in schemes that claim to illustrate immunological and inflammatory mechanisms of the airway mucosa in vivo.
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| 8. |
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| 9. |
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| 10. |
- Persson, Carl, et al.
(författare)
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Plasma-derived proteins in airway defence, disease and repair of epithelial injury
- 1998
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Ingår i: European Respiratory Journal. - 1399-3003. ; 11:4, s. 958-970
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Tidskriftsartikel (refereegranskat)abstract
- One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.
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