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Biomedical subjects

C G Persson

Publications and source records attributed to C G Persson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Eosinophils, neutrophils, and venular gaps in the airway mucosa at epithelial removal-restitution.

Shedding of epithelium, increased venular permeability, and traffic of activated eosinophils and neutrophils may characterize asthmatic airways. This in vivo study involving briefly anesthetized guinea pigs examines whether epithelial denudation itself affects airway venules and granulocytes. Using an oral probe, a de-epithelialized tracheal zone (0.8 x 30 mm) was produced without bleeding or damage to the basement membrane. After 10 min, 2, 8, and 48 h, the tracheal tissue was examined by scanning and transmission electron microscopy. Silver staining revealed endothelial cell borders. Histochemistry identified neutrophils and eosinophils. Confirming previous observations, epithelial restitution started promptly and occurred speedily under a plasma exudation-derived, leukocyte-rich gel. Ten minutes after de-epithelialization, venular gaps (silver dots) were recognized as plasma exudation sites and, separately, silver rings at endothelial cell borders indicated attachment and extravasation of leukocytes. Tissue neutrophils were increased from 10 min to 48 h. Normally occurring eosinophils decreased in numbers during re-epithelialization, partly due to migration into the airway lumen and local cell death. Clusters of extracellular eosinophil granules were increased from 10 min to 8 h. Gentle removal of airway epithelium thus produced venular gaps, infiltration of neutrophils, and migration, activation, and death of eosinophils. Epithelial shedding-restitution processes may cause part of the microvascular and leukocyte changes that occur in inflammatory airway diseases.

Animals↗
PubMed1996

Day-night differences in mucosal plasma proteins in common cold.

Aggravation of symptoms in inflammatory airway diseases is common in the early morning hours, but little is known about day-night differences in the occurrence of plasma exudate on the airway surface. We have therefore examined the plasma macromolecules on the nasal mucosa at different time points. The study comprised 20 subjects who had been inoculated (day 0) with coronavirus intranasally. Ten subjects remained healthy and 10 developed common cold with significant symptoms from day 2 to day 6. Starting on day 3 at 8.00 h and repeated at 4 h intervals until 4.00 h on day 4, nasal lavages were carried out by employment of a nasal pool-device which fills the entire unilateral nasal cavity and gently but effectively irrigates its surface. Lavage fluid levels of albumin (Mw 69,000 D) and fibrinogen (Mw 340,000 D) were determined. In the healthy subjects the levels of albumin and fibrinogen remained low throughout the experiment, however, with mean peak values of the two proteins occurring at 4.00 h (p < 0.05 compared to daytime nadir at 16.00 h). In subjects with common cold both albumin (p < 0.05) and fibrinogen (p < 0.01) exhibited marked variation with individual and mean peak levels recorded at 8.00 h day 3, and 4.00 h day 4. These mean peak values were 5-20 times higher (p < 0.01 - p < 0.05) than the mean levels recorded in these subjects at the other time periods. The present data indicate a marked day-night difference in the occurrence of plasma proteins on the airway surface in common cold, whereas in health the difference is much less. We conclude that different-sized plasma proteins may accumulate on the mucosa in healthy airways during late night hours and that in common cold this nocturnal accumulation may be considerably increased.

Adult↗
PubMed1996

Exudative and absorptive permeability in different phases of an experimental colitis condition.

BACKGROUND: Increased intestinal 'permeability' in inflammatory bowel disease and in animal models of this disease has been reported. This study asks if permeability changes are bidirectional and parallel cellular inflammation. METHODS: In rats acute inflammatory cell infiltration (ICI) was induced in an excluded bowel loop by instillation of 4% acetic acid. Plasma exudation was investigated by intravenous infusion of 125I-albumin and determination of radioactivity in loop perfusates. Absorption was measured by placing 51Cr-ethylenediaminetetraacetic acid in the loop and counting total radioactivity appearing in urine over 24 h. RESULTS: Acute ICI was induced with acetic acid on day 4 but, as judged by ICI and histology, recovered by day 14. Acetic acid treatment resulted in increased absorption on day 4, which return to control levels by day 14. Acetic acid treatment resulted in increased plasma exudation on day 4, which remained increased on day 14. CONCLUSION: Absorption and exudation changes are not necessarily bidirectional, and ICI may not be required for significant and sustained plasma exudation to take place. We suggest that the exudative response reflects a 'functional inflammation' that may occur and be important also in the absence of the traditional indices of bowel inflammation.

Acetic Acid↗
PubMed1995

In vivo restitution of airway epithelium.

Epithelial shedding occurs in health and, extensively, in inflammatory airway diseases. This study describes deepithelialisation, reepithelialisation and associated events in guinea-pig trachea after shedding-like epithelial denudation in vivo. Mechanical deepithelialisation of an 800-microns wide tracheal zone was carried out using an orotracheal steel probe without bleeding or damage to the basement membrane. Reepithelialisation was studied by scanning- and transmission electron microscopy and light microscopy. Nerve fibres were examined by immunostaining. Cell proliferation was analysed by [3H]-thymidine autoradiography. Immediately after epithelial removal secretory and ciliated (and presumably basal) epithelial cells at the wound margin dedifferentiated, flattened and migrated rapidly (2-3 microns/min) over the denuded basement membrane. Within 8-15 h a new, flattened epithelium covered the entire deepithelialised zone. At 30 h a tight epithelial barrier was established and after 5 days the epithelium was fully redifferentiated. After completed migration an increased mitotic activity occurred in the epithelium and in fibroblasts/smooth muscle beneath the restitution zone. Reinnervating intraepithelial calcitonin gene-related peptide-containing nerve fibres appeared within 30 h. We conclude that (1) reproducible shedding-like denudation, without bleeding or damage to the basement membrane, can be produced in vivo; (2) secretory and ciliated cells participate in reepithelialisation by dedifferentiation and migration; (3) the initial migration is very fast in vivo; (4) shedding-like denudation may cause strong secretory and exudative responses as well as proliferation of epithelium, and fibroblasts/smooth muscle. Rapid restitution of airway epithelium may depend on contributions from the microcirculation and innervation.

Animals↗
PubMed1995

Allergen challenge-induced entry of alpha 2-macroglobulin and tryptase into human nasal and bronchial airways.

BACKGROUND: Microvascular-epithelial exudation of bulk plasma may characterize inflammatory airway diseases. This study compares the acute allergen challenge-induced mast cell and exudative responses in nasal and bronchial airways. The focus is on alpha 2-macroglobulin as an index of luminal entry of plasma exudates. METHODS: Separate nasal and bronchial allergen challenges were carried out outside the pollen season in eight patients with pollen-induced seasonal allergic rhinitis. The levels of different-sized plasma proteins (albumin molecular weight, 66,000 d and alpha 2-macroglobulin molecular weight, 725,000 d) and tryptase were determined in pre- and postchallenge nasal lavage and bronchoalveolar lavage (BAL) fluids. Diluent and increasing doses of allergen were sprayed into the right nasal cavity, and each challenge was followed by a nasal lavage (volume, 15 ml) with a "nasal pool" device (recovery, > 80%). Endobronchial allergen challenge (individual doses) and BAL (volume, 2 x 25 ml) were performed in a lobe bronchus through a fiberoptic bronchoscope (recovery, 30%). Saline challenge and BAL were carried out in the contralateral lung as control. RESULTS: The levels of albumin, alpha 2-macroglobulin, and tryptase increased dose-dependently in postchallenge nasal lavage fluids (p < 0.05) and correlated to nasal symptoms. In particular, albumin and alpha 2-macroglobulin correlated (r = 0.98, p < 0.001). Both alpha 2-macroglobulin and tryptase, but not albumin, were increased in BAL fluids from the allergen-challenged side (p < 0.05). CONCLUSION: Local allergen challenge causes luminal entry of tryptase and alpha 2-macroglobulin in the nose and bronchi of patients with allergy. We suggest that mast cell and plasma exudation responses may be similar in human nasal and bronchial airways and that albumin levels (in BAL fluids) may not well reflect the exudation process in bronchial airways.

Adult↗
PubMed1995

Loratadine reduces allergen-induced mucosal output of alpha 2-macroglobulin and tryptase in allergic rhinitis.

BACKGROUND: Despite the wide use of antihistamines in the treatment of allergic rhinitis, little is known about effects of these drugs on airway mucosal indices, which specifically reflect either mast cell release activity (tryptase) or microvascular-epithelial exudation of bulk plasma (alpha 2-macroglobulin). OBJECTIVE: This study, involving subjects with seasonal allergic rhinitis, examines the effects of loratadine treatment on allergen-induced nasal mucosal output of tryptase and alpha 2-macroglobulin. Effects on nasal symptoms and eosinophils are also examined. METHODS: Placebo and loratadine (20 mg) were given orally once daily for 5 days at 6-week intervals. Nasal diluent and allergen challenges were carried out on day 5. The mucosa was lavaged with saline solution after each challenge, and nasal lavage fluid levels of tryptase and alpha 2-macroglobulin were determined. Nasal symptoms were scored, and nasal peak expiratory flow rates were measured. Superficial cells (eosinophils) were obtained with a brush device before and 24 hours after the allergen challenges. RESULTS: Allergen dose-dependently increased the nasal symptoms and the lavage fluid levels of alpha 2-macroglobulin and tryptase. Allergen also reduced the nasal peak expiratory flow rates. Loratadine inhibited the exudation of alpha 2-macroglobulin and reduced tryptase levels, nasal symptoms, and obstruction, but did not affect the number of eosinophils. CONCLUSION: The inhibitory effects of loratadine on nasal lavage fluid levels of alpha 2-macroglobulin suggest that histamine, through effects on microvascular H1-receptors, mediates allergen challenge-induced exudation of bulk plasma in acute allergic rhinitis. The reduced lavage fluid levels of tryptase suggest either that loratadine directly attenuates mast cell release activity or that loratadine, through inhibition of the exudation process, simply attenuates luminal entry of tissue solutes (in this case, tryptase).

Adolescent↗
PubMed1995

Exudative hyperresponsiveness of the airway microcirculation in seasonal allergic rhinitis.

BACKGROUND: Mucosal exudation of plasma is a non-injurious, physiological response of the airway microcirculation to different inflammatory processes. The exudative response is similar in the nose and bronchi and exudation occurs in both allergic asthma and rhinitis. The exudative response is a specific end-organ function of the mucosal microcirculation that may be altered in airway diseases. OBJECTIVE: This study examines the hypothesis of altered responsiveness of the superficial airway microcirculation to vascular permeability-increasing challenges in sustained allergic inflammation. METHODS: Fourteen patients with birch-pollen induced allergic rhinitis were studied for 7 weeks during a Swedish birch-pollen season. Nasal symptoms (itching, sneezing, blockage, and discharge) were recorded and the occurrence of pollen was determined. The plasma exudation response was examined by topical histamine challenges at the end (May) and well out of (December) the season. Challenge and lavage were carried out concomitantly using a 'nasal pool'-device. The unilateral nasal cavity was filled for consecutive 10 minute periods with saline and two concentrations of histamine (80 micrograms/mL and 400 micrograms/mL). The lavage fluid levels of different-sized plasma proteins (albumin-66,000 D, fibrinogen-340,000 D, and alpha 2-macroglobulin-725,000 D) were determined. RESULTS: The pollen season was mild resulting in only minor nasal symptoms. Histamine produced exudation of all plasma proteins across the microvascular epithelial barriers with particularly strong correlation between the levels of albumin and alpha 2-macroglobulin (r = 0.98; P < 0.001). The exudative response to histamine was concentration-dependent (P < 0.05) and, furthermore, it was significantly greater late into the season compared with outside the pollen season (albumin: P < 0.05, fibrinogen; P < 0.05, alpha 2-macroglobulin: P < 0.01). CONCLUSION: We conclude that histamine produced concentration-dependent nasal airway exudation of bulk plasma in subjects with seasonal rhinitis and that this response is abnormally great during the pollen season. Whether angiogenesis or increased responsiveness of the microvascular endothelium may explain this phenomenon now remains unknown. We suggest that a microvascular exudative hyperresponsiveness may characterize allergic airway disease.

Adult↗
PubMed1995

Nasal cytokines in common cold and allergic rhinitis.

Coronavirus-induced common cold and allergen-induced rhinitis are characterized by nasal mucosal exudation of bulk blood plasma. The mucosal exudation process involves 'flooding' of the lamina propria with plasma-derived binding proteins and it is possible that subepithelial inflammatory cytokines and mediators may be moved by the exudate to the mucosal surface. In this study, we have analysed cytokine levels in nasal lavage (NAL) fluids from non-allergic subjects inoculated with coronavirus (n = 20) and from subjects with allergic (birch pollen) rhinitis subjected to additional allergen challenge (samples were obtained 35 min post challenge) in the laboratory (n = 10). Ten of the 20 inoculated subjects developed common cold and 10 remained healthy. Interferon-gamma (IFN gamma), interleukin-1 beta (IL-1 beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL-6 were analysed in unprocessed NAL fluids using immunoassays. The subjects who developed common cold had increased NAL fluid levels of IFN gamma (P < 0.05) that correlated well with the symptoms (P < 0.001). IFN gamma did not increase in subjects with allergic rhinitis. IL-1 beta levels were similar in NAL fluids obtained from all inoculated subjects. In the subjects with allergic rhinitis NAL fluid levels of both IL-1 beta and GM-CSF were increased (P < 0.05). GM-CSF was not detected in common cold. IL-4 and IL-6 were not detectable in any of the NAL fluids. The present cytokines may not only emanate from superficial mucosal cells. By aiding plasma exudation subepithelial cytokines may potentially also be retrieved on the mucosal surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Epithelial pathways for luminal entry of bulk plasma.

Inflammatory challenges of the airway mucosa cause luminal entry of bulk plasma. Extravasation of plasma is well described but the routes for epithelial passage of plasma are largely unknown. Using colloidal gold (5 nm) as tracer we have now examined the fate of extravasated plasma in the airways. The tracer was given intravenously to anaesthetized, ovalbumin-sensitized guinea-pigs 2 min prior to airway mucosal challenge with 12 pmol ovalbumin (the dose was selected from a separate dose-response study). Tissue specimens were collected 30 s, 3 and 6 min after end of challenge (separate time course experiments suggested that the peak rate of entry of plasma occurred at about 5 min). The colloidal gold particles were visualized by autometallographic silver intensification. The gold produced no circulatory disturbance and had a uniform vascular distribution with negligible adherence to vascular endothelium. After challenge gold was first widely distributed in the lamina propria. At 3 and 6 min the tracer was also in the epithelium and airway lumen. It appeared that plasma was moved distinctly between and all around each epithelial cell. Bright field-, scanning-, and transmission electron-microscopy indicated that the luminal entry of plasma did not affect the integrity of the epithelial lining. This study demonstrates that the plasma exudate moves across an intact epithelial layer through ubiquitous paracellular pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1995

Topical nitroprusside may reduce histamine-induced plasma exudation in human nasal airways.

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.

Administration, Topical↗
PubMed1995

Antiallergic actions of high topical doses of terbutaline in human nasal airways.

It is debatable whether beta 2-receptor agonists produce antiallergic effects in human airways. This question has been addressed in the present study by examination of both mast-cell indices and the physiologic response to allergen challenge in human nasal airways. Twelve asymptomatic patients with seasonal allergic rhinitis were investigated outside the pollen season. Intranasal allergen provocation was carried out with diluent and three increasing doses of allergen. Topical terbutaline sulfate (1.0 mg) was given 5 min prior to each allergen challenge and nasal lavage was carried out 10 min after each challenge. The study design was double-blind, placebo-controlled, crossover, and randomized. The allergen challenge-induced mast-cell activation and the ensuing physiologic response of the airway tissue were investigated by measuring a mast-cell-derived mediator (tryptase) and plasma proteins (albumin and alpha 2-macroglobulin), respectively, in the lavage fluids. Allergen provocation produced dose-dependent increments of nasal symptoms and lavage fluid levels of tryptase, albumin and alpha 2-macroglobulin. Both nasal symptoms (P < 0.05) and lavage fluid levels of tryptase (P < 0.05), albumin (P < 0.05), and alpha 2-macroglobulin (P < 0.01) were reduced by pretreatment with topical terbutaline sulfate. We conclude that high doses of topical terbutaline may produce significant antiallergic effects in human airways by equally reducing both tryptase release and plasma exudation in the acute allergic reaction in human airways. Further studies are now warranted to determine whether microvascular antipermeability effects of beta 2-receptor stimulation contribute to the present observations.

Administration, Topical↗
PubMed1995

Effects of topical capsaicin in seasonal allergic rhinitis.

BACKGROUND: Mucosal exudation (luminal entry) of bulk plasma is a key feature of airway defence and inflammation. In guinea pig and rat airways this response is readily produced by neurogenic irritants, notably capsaicin. Thus "neurogenic airway inflammation" has become an established concept. The present study examines whether capsaicin also produces mucosal exudation of plasma in human nasal airways both in health and disease (seasonal allergic rhinitis). METHODS: Pain-producing concentrations of capsaicin (30-300 ng/ml) were applied to the nasal mucosal surface both before and late into the pollen season. Levels of albumin in nasal lavage fluid were measured as an index of mucosal exudation of plasma. In a separate group of patients with seasonal allergic rhinitis nasal challenge with an exudative concentration of histamine was carried out before the birch pollen season and concentrations of albumin in lavage fluid were measured. RESULTS: Pollen counts and symptom scores revealed a mild pollen season. Capsaicin produced considerable nasal pain and this response was augmented late into the season when capsaicin also produced nasal blockage. However, capsaicin failed to produce any mucosal exudation of plasma either before or late into the pollen season. The exudative effect of histamine was confirmed. CONCLUSIONS: The augmented pain response to capsaicin suggests that a sensory nerve hyperresponsiveness may characterise allergic airways disease. In contrast to the effects on animal airways, capsaicin failed to produce mucosal exudation of plasma in the human nasal airway. The animal based neurogenic inflammation concept is therefore not valid for the human nasal airway, not even in inflamed airways when a neural hyperresponsiveness has developed.

Administration, Topical↗
PubMed1995

Effects of topical budesonide on epithelial restitution in vivo in guinea pig trachea.

BACKGROUND: Continuous epithelial shedding and restitution processes may characterise the airways in diseases such as asthma. Epithelial restitution involves several humoral and cellular mechanisms that may potentially be affected by inhaled anti-asthma drugs. The present study examines the effect of a topical steroid on epithelial restitution in vivo in the guinea pig. METHODS: The airway epithelium was mechanically removed from well defined areas of guinea pig trachea without surgery and without damage to the basement membrane or bleeding. An anti-inflammatory dose of budesonide (1 mg) was administered repeatedly to the tracheal surface by local superfusion 24 hours before, at (0 hours), and 24 hours after the denudation. Migration of epithelial cells, formation of a plasma exudation-derived gel, and appearance of luminal leucocytes were recorded by scanning electron microscopy. Cell proliferation was visualised by bromodeoxyuridine immunohistochemistry and tissue neutrophils and eosinophils by enzyme histochemistry. RESULTS: Immediately after creation of the denuded zone ciliated and secretory cells on its border dedifferentiated, flattened out, and migrated speedily (mean (SE) 2.3 (0.3) micron/min) over the basement membrane. After 48 hours the entire denuded zone (800 microns wide) was covered by a tightly sealed epithelium; at this time increased proliferation was observed in new and old epithelium and subepithelial cells. Budesonide had no detectable effect on epithelial dedifferentiation, migration, sealing, or proliferation. Immediately after denudation and continuously during the migration phase plasma was extravasated creating a fibrinous gel rich in leucocytes, particularly neutrophils, over the denuded area. Budesonide had no effect on either the gel or the leucocyte density. CONCLUSIONS: These observations suggest that topical glucocorticoids may not interfere with a fast and efficient restitution of the epithelium in the airways.

Administration, Topical↗
PubMed1994

Microcirculation-derived factors in airway epithelial repair in vivo.

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.

Animals↗