| 1. |
- Greiff, Lennart, et al.
(författare)
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Effects of topical platelet activating factor on the guinea-pig tracheobronchial mucosa in vivo
- 1997
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 160:4, s. 387-391
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Tidskriftsartikel (refereegranskat)abstract
- Platelet activating factor (PAF) has been reported to produce a variety of airway effects including epithelial damage and increased airway-lung absorption of hydrophilic tracers. The present study examines effects of PAF on the guinea-pig tracheobronchial mucosa in vivo. Vehicle with and without PAF (4.0 and 8.0 nmol) was superfused onto the tracheobronchial mucosa. The levels of 125I-albumin, previously given intravenously, were determined in tracheobronchial lavage fluids as an index of mucosal exudation of plasma. The mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA (a low molecular weight, 492 Da, hydrophilic tracer) was superfused onto the mucosal surface through an oro-tracheal catheter, together with vehicle or PAF (8.0 nmol). A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of mucosal absorption. PAF produced dose-dependent mucosal exudation of plasma up to 20-fold greater than control (P < 0.001). However, PAF did not damage the epithelium and the absorption ability of the airway mucosa was unaffected. The results, in contrast to previous reports, suggest that PAF may not readily damage the airway mucosa even at large exudative doses of the agent. The present finding support the view that the plasticity of the epithelial junctions allows the creation of valve-like paracellular pathways for unidirectional clearance of extravasated plasma into the airway lumen. We suggest that endogenous PAF may participate in first line respiratory defence reactions by causing lumenal entry of bulk plasma without harming the epithelium.
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| 2. |
- Greiff, Lennart, et al.
(författare)
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Effects of hydrogen peroxide on the guinea-pig tracheobronchial mucosa in vivo
- 1999
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 165:4, s. 415-420
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Tidskriftsartikel (refereegranskat)abstract
- Lumenal entry of plasma (mucosal exudation) is a key feature of airway inflammation. In airways challenged with histamine-type mediators and allergen the mucosal exudation response occurs without causing epithelial derangement and without increased airway absorption. In contrast, reactive oxygen metabolites may cause mucosal damage. In this study, involving guinea-pig airways, we have examined effects of H2O2 on airway exudation and absorption in vivo. Vehicle or H2O2 (0.1 and 0.5 M) was superfused onto the tracheobronchial mucosal surface through an oro-tracheal catheter. 125I-albumin, given intravenously, was determined in tracheobronchial tissue and in lavage fluids 10 min after challenge as an index of mucosal exudation of plasma. The tracheobronchial mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA was superfused 20 min after vehicle or H2O2 (0.1 and 0.5 M) had been given. A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of airway absorption. The high dose of H2O2 (0.5 M) produced epithelial damage, increased the absorption of 99mTc-DTPA (P < 0.001), and increased the exudation of plasma (P < 0.001). Notably, it appeared that all extravasated plasma had entered the airway lumen within 10 min. These data demonstrate that H2O2 differs from exudative autacoids such as histamine by causing both epithelial damage and plasma exudation responses. These data also agree with the view that the epithelial lining determines the rate of absorption and is responsible for the valve-like function that allows lumenal entry of extravasated bulk plasma without any increased inward perviousness.
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| 3. |
- Erjefält, Jonas, et al.
(författare)
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Microcirculation-derived factors in airway epithelial repair in vivo
- 1994
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 48:2, s. 161-178
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Tidskriftsartikel (refereegranskat)abstract
- Airway epithelial repair, by cell migration over a denuded, intact basement membrane, occurs rapidly in vivo. The present study examines microcirculation-derived factors in the reepithelialization process in the guinea pig. A well-defined tracheal zone was gently deepithelialized; no bleeding occurred and the basement membrane was left intact. Plasma exudation was visualized by use of iv colloidal gold (diameter: 5 nm) or fluoresceinisothiocyanate-labeled dextran. Scanning and transmission electron microscopy confirmed the migration of epithelial cells and, additionally, allowed us to examine the presence of an extracellular matrix gel and leukocytes on the denuded basement membrane. Fibronectin was analyzed by immunocytochemistry. Following epithelial removal plasma promptly extravasates and produces a fibrin-fibronectin gel to cover the denuded basement membrane. Epithelial cells dedifferentiate, flatten, and migrate rapidly (several micron/min) beneath the plasma-derived gel. Within 30 min the gel contains numerous leukocytes, some of which are eosinophils. Plasma exudes into the gel until about 8 hr by which time the entire denuded zone (800 microns) is covered by squamous epithelium. The fibrin-fibronectin gel is suggested to be exclusively plasma-derived. In conclusion, reepithelialization in vivo occurs beneath a gel containing adhesive plasma proteins and leukocytes. We suggest that a plasma exudate provides immediate cover of denuded airway basement membrane and that plasma- and leukocyte-derived factors contribute essentially to reepithelialization in vivo.
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| 4. |
- Erjefält, Jonas, et al.
(författare)
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Mucosal nitric oxide may tonically suppress airways plasma exudation
- 1994
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 150:1, s. 227-232
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Tidskriftsartikel (refereegranskat)abstract
- In a search for airway epithelial mechanisms that may affect the subepithelial microcirculation, we examined plasma exudation responses to NG-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. L-NAME was applied topically on the tracheal mucosa of guinea pigs that had previously received 125I-albumin and/or colloidal gold particles (5 nm) intravenously. Luminal entry of plasma was determined by the levels of 125I-albumin in tracheal lavage fluid. Topical L-NAME (2.2, 9, and 22 mumol), but not intravenous L-NAME (375 mumol/kg), produced plasma exudation into the airway lumen (p < 0.01 to p < 0.001). The L-NAME enantiomer NG-nitro-D-arginine-methyl ester (D-NAME, 9 mumol) produced no exudative response. Coadministration of L-arginine (27 mumol) abolished the L-NAME-induced exudation. The extravasated plasma was distributed in the lamina propria and between epithelial cells (colloidal gold). The epithelial surface structure (scanning electron microscopy) appeared intact. Staining with nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase suggested that epithelial basal may contain nitric oxide synthases. We suggest that endogenously released nitric oxide from epithelial or other superficial cells tonically suppresses the macromolecular permeability of the subepithelial microcirculation.
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| 5. |
- Greiff, Lennart, et al.
(författare)
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Topical nitroprusside may reduce histamine-induced plasma exudation in human nasal airways
- 1995
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 50:7, s. 593-597
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal exudation of nonsieved bulk plasma is a key feature of airway defense and inflammation. We have previously observed in guinea pig tracheobronchial airways that endogenous nitric oxide (NO) of the mucosa may tonically suppress the permeability of the subepithelial microcirculation, and that topical administration of the NO donor nitroprusside may reduce plasma exudation responses. The present study examines whether nitroprusside affects histamine-induced mucosal exudation of plasma in the human nasal airway. In a dose-finding tolerability experiment, using changes in nasal patency as response, placebo and nitroprusside (1.2 and 3.6 mg per nasal cavity) were applied on the mucosal surface with a nasal-spray device. Nasal peak expiratory flow (PEF) rates were measured before the application and thereafter every third minute for 15 min. Nitroprusside produced a dose-dependent decrease in nasal PEF rates compared to placebo. Placebo or nitroprusside (7.2 mg) was then given to the right nasal cavity, followed 3 min later by challenge with saline or histamine (600 micrograms). The drug and the challenge were both applied with a nasal-spray device. With a nasal pool-device, the same large part of the nasal mucosal surface was lavaged before and after the treatment/challenge. The lavage fluid levels of alpha 2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. The histamine-induced lavage fluid level of alpha 2-macroglobulin was significantly higher after treatment with placebo than with nitroprusside. The present data indicate that nitroprusside may have antiexudative effects in human airways. Hence, unlike other microvascular permeability active agents, this pharmacologic principle may be active in both guinea pig and human airways.
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| 6. |
- Persson, Carl, et al.
(författare)
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Airway permeability
- 1995
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222. ; 25:9, s. 807-814
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Forskningsöversikt (refereegranskat)
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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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