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Biomedical subjects

C G Persson

Publications and source records attributed to C G Persson.

At least 19 recordsLinked to original sources
PubMed2000

Role of macrophage migration inhibitory factor (MIF) in allergic and endotoxin-induced airway inflammation in mice.

Macrophage migration inhibitory factor (MIF) has recently been forwarded as a critical regulator of inflammatory conditions, and it has been hypothesized that MIF may have a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Hence, we examined effects of MIF immunoneutralization on the development of allergen-induced eosinophilic inflammation as well as on lipopolysaccharide (LPS)-induced neutrophilic inflammation in lungs of mice. Anti-MIF serum validated with respect to MIF neutralizing capacity or normal rabbit serum (NRS) was administered i.p. repeatedly during allergen aerosol exposure of ovalbumin (OVA)-immunized mice in an established model of allergic asthma, or once before instillation of a minimal dose of LPS into the airways of mice, a tentative model of COPD. Anti-MIF treatment did not affect the induced lung tissue eosinophilia or the cellular composition of bronchoalveolar lavage fluid (BALF) in the asthma model. Likewise, anti-MIF treatment did not affect the LPS-induced neutrophilia in lung tissue, BALF, or blood, nor did it reduce BALF levels of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-1alpha (MIP-1alpha). The present data suggest that MIF is not critically important for allergen-induced eosinophilic, and LPS-induced neutrophilic responses in lungs of mice. These findings do not support a role of MIF inhibition in the treatment of inflammatory respiratory diseases.

Animals↗
PubMed2000

Effects of benzalkonium chloride on innate immunity physiology of the human nasal mucosa in vivo.

OBJECTIVE: Benzalkonium chloride (BC) is a preservative commonly used in nasal decongestant sprays. It has been suggested that BC may be harmful to the nasal mucosa. The present study, involving healthy volunteers, examines effects of BC on nasal mucosal end-organ functions. METHODS: Isotonic saline and BC (0.1 mg/mL) were administered acutely to the nasal mucosa using a nasal pool device. Nasal symptoms were determined. Nasal lavage fluid levels of alpha2-macroglobulin and fucose were measured as indices of plasma exudation and glandular secretion, respectively. In addition, BC (0.1 mg/mL) was given as single actuations of 100 microL per nasal cavity three times daily for 10 days. The ability of histamine (0.4 mg/mL) to evoke nasal symptoms and plasma exudation responses was determined before and after the repeated BC administration series. RESULTS: BC produced immediate nasal smart or pain (P < .05), but tolerance to this response developed by repeated administrations. BC increased nasal mucosal output of fucose (P < .05), whereas nasal lavage fluid levels of alpha2-macroglobulin were unaffected. Histamine produced significant symptoms and mucosal exudation of alpha2-macroglobulin (P values < .01), equally before and after the 10 days of BC exposure. CONCLUSIONS: BC in dosages commonly used as preservative in nasal decongestant sprays produced short-term glandular secretion and nasal smart or pain. However, 10 days' frequent exposure to BC was not associated with untoward symptomatic effects, nor was a sensitive mucosal variable such as histamine-induced exudative responsiveness affected by this repeated exposure 1 BC.

Administration, Topical↗
PubMed1999

Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice.

The earliest contact between antigen and the innate immune system is thought to direct the subsequent antigen-specific T cell response. We hypothesized that cells of the innate immune system, such as natural killer (NK) cells, NK1.1(+) T cells (NKT cells), and gamma/delta T cells, may regulate the development of allergic airway disease. We demonstrate here that depletion of NK1.1(+) cells (NK cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3(+) T cell infiltration as well as increased levels of interleukin (IL)-4, IL-5, and IL-12 in bronchoalveolar lavage fluid in a murine model of allergic asthma. Moreover, systemic allergen-specific immunoglobulin (Ig)E and IgG2a levels and the number of IL-4 and interferon gamma-producing splenic cells were diminished in mice depleted of NK1.1(+) cells before the priming regime. Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation. CD1d1 mutant mice, deficient in NKT cells but with normal NK cells, developed lung tissue eosinophilia and allergen-specific IgE levels not different from those observed in wild-type mice. Mice deficient in gamma/delta T cells showed a mild attenuation of lung tissue eosinophilia in this model. Taken together, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and that this effect of NK cells is exerted during the immunization. If translatable to humans, these data suggest that NK cells may be critically important for deciding whether allergic eosinophilic airway disease will develop. These observations are also compatible with a pathogenic role for the increased NK cell activity observed in human asthma.

Allergens↗
PubMed1999

Experimental common cold increases mucosal output of eotaxin in atopic individuals.

BACKGROUND: In view of recent observations demonstrating that rhinovirus infections are associated with increased local activity of eosinophils, we hypothesized that eotaxin, a selective eosinophil chemoattractant, may be involved in eosinophil recruitment/activation in common cold infections. METHODS: Twenty-three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 (HRV 16) outside the pollen season. Sequential diluent and allergen (10(3) SQ-U) challenges, each followed by nasal lavage, were carried out about 3 months before and 4 days after virus inoculation. RESULTS: Seventeen patients developed common cold and were further analyzed. Lavage fluid levels of eotaxin were increased at the height of active common cold (day 4 after inoculation) both at baseline (after diluent challenge) (P<0.01) and acutely after allergen challenge (P<0.05). CONCLUSIONS: Common cold symptoms after nasal HRV 16 inoculation are associated with increased nasal mucosal output of eotaxin, suggesting that this chemokine is partly responsible for recruitment/activation of airway mucosal eosinophils in common cold infections.

Blood Proteins↗
PubMed1999

Circulating eosinophil/basophil progenitors and nasal mucosal cytokines in seasonal allergic rhinitis.

Accumulation of eosinophils in the airways is characteristic of allergic rhinitis and asthma. The tissue eosinophilia may involve both recruitment of mature eosinophils and proliferation of their progenitors. This study examines mature eosinophils (nasal and circulating), their circulating progenitors, and a potential role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in stimulating these progenitors. Twelve subjects with a history of seasonal allergic rhinitis and positive skin prick test for birch pollen were studied during four periods: shortly before, in the early and intense phase, at the end, and well after the Swedish birch-pollen season. Nasal mucosal and circulating eosinophils were examined in both nasal brushings and peripheral blood samples. Eosinophil/basophil progenitors were determined by counting colony-forming units in nonadherent mononuclear blood-cell cultures in methylcellulose at 14 days. The nasal mucosal cytokines GM-CSF, interleukin (IL)-1beta, IL-3, IL-5, IL-6, IL-8, and RANTES were analyzed (ELISA) in nasal lavage (NAL) fluids. All patients developed severe symptoms of rhinitis at the height of the season, with increased numbers of eosinophils in the nasal mucosa (P<0.05) and in the circulation (P<0.05). At this time point, the number of circulating progenitors (P<0.05) and the NAL fluid level of GM-CSF (P<0.05) were also increased. In contrast, there was no change in the NAL fluid levels of IL-1beta, IL-3, IL-6, or IL-8. Neither IL-5 nor RANTES could be detected in any of the NAL fluids. At the end of or after the season, there was no increase in nasal eosinophils or circulating eosinophils or progenitors (P>0.05). Ex vivo addition of GM-CSF (10-100 U) increased the number of blood progenitors grown before (P<0.01) and after (P<0.05) the season, compared with during the season. The in vitro GM-CSF responsiveness of progenitors may be related to whether or not these already have been stimulated endogenously by GM-CSF. Taken together, our data thus suggest that GM-CSF may play a role in vivo to increase production of eosinophilic progenitors in allergic airway disease.

Adult↗
PubMed1999

Effects of hydrogen peroxide on the guinea-pig tracheobronchial mucosa in vivo.

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.

Albumins↗
PubMed1999

Demonstration of bronchial eosinophil activity in seasonal allergic rhinitis by induced plasma exudation combined with induced sputum.

BACKGROUND: Patients with seasonal allergic rhinitis may develop bronchial hyperresponsiveness during the active disease period. Eosinophil activation may occur in the bronchial mucosa and may be reflected by increased sputum levels of eosinophil cationic protein (ECP), especially when ECP binding proteins such as alpha 2-macroglobulin pass through the lamina propria and across the epithelium into the airway lumen. A study was therefore undertaken to determine histamine airway responsiveness (FEV1) and bronchovascular responsiveness (exudation of alpha 2-macroglobulin) to histamine in subjects with seasonal allergic rhinitis, and to explore whether sputum ECP levels are increased by the use of induced exudation followed by induced sputum. METHODS: Eleven patients with seasonal allergic rhinitis were examined before and during a birch pollen season. Sputum was induced by inhalation of 4.5% saline twice before and twice during the pollen season. Histamine inhalations were given before the second of each pair of sputum inductions at increasing concentrations until FEV1 was reduced by 20%. Sputum levels of alpha 2-macroglobulin and ECP were determined as indices of bronchial exudation of plasma and activation of bronchial eosinophils, respectively. RESULTS: Bronchomotor responsiveness increased during the pollen season (median difference in the reduction of FEV1 9% (95% confidence interval (CI) -3 to 26)) but histamine induced exudation of plasma was not increased. Baseline sputum levels of alpha 2-macroglobulin and ECP did not increase. Histamine induced exudation of alpha 2-macroglobulin was associated with increased sputum levels of ECP exclusively during the pollen season (median difference 8.2 ng/ml (95% CI 0.4 to 562.0)). CONCLUSION: Bronchial hyperresponsiveness in seasonal allergic rhinitis may not be associated with bronchovascular exudative hyperresponsiveness. Sputum levels of ECP were increased only during the season, and only after induced exudation (potentially moving ECP to the mucosal surface). It is suggested that the combined method of induced exudation and induced sputum may significantly improve the yield of some markers of inflammation in sputum samples.

Adult↗
PubMed1999

Lack of systemic anaphylaxis and aeroallergen-induced airway plasma extravasation in allergic immunoglobulin-deficient mice.

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.

Acute-Phase Reaction↗
PubMed1999

Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways.

Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of allergic airway diseases such as rhinitis and asthma. To explore the cellular mechanisms behind eosinophil granule release in human allergic airways, 16 symptom-free patients with seasonal allergic rhinitis were challenged daily with allergen during 1 wk. Nasal lavage samples and biopsies, obtained before and 24 h after the last allergen exposure, were processed for immunohistochemical and electron microscopic analysis. The allergen challenges produced nasal symptoms, marked tissue eosinophilia, and an increase in lavage fluid levels of eosinophil cationic protein (ECP). The nasal mucosa areas with intense extracellular immunoreactivity for ECP were associated with abundant free eosinophil granules. Electron microscopy confirmed the free granules and revealed that all mucosal eosinophils were involved in granule release, either by cytolysis (33%) or piecemeal degranulation (PMD) (67%). Resting or apoptotic eosinophils were not observed. Cytolytic eosinophils had less signs of intracellular granule release (p < 0. 001) and a higher content of intact granules (p < 0.001) compared with viable eosinophils in the same tissue. This study demonstrates eosinophil cytolysis (ECL) as a distinct mechanism for granule mediator release in human allergic airway mucosa. The nature and extent of the ECL and its product (i.e., protein-laden extracellular granules) indicate that allergen-induced cytolysis is a primary and major mechanism for the release of eosinophil proteins in human allergic airway inflammation in vivo.

Adolescent↗
PubMed1999

Allergen challenge-induced acute exudation of IL-8, ECP and alpha2-macroglobulin in human rhinovirus-induced common colds.

Rhinovirus infections cause exacerbations of eosinophilic airway disease. The acute effects of allergen-challenge on nasal interleukin-8 (IL-8), eosinophil cationic protein (ECP), and alpha2-macroglobulin were examined in atopic subjects with common cold symptoms. Twenty-three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 outside the pollen season. Diluent and allergen challenges, followed by nasal lavages, were carried out about 3 months before and 4 days after virus inoculation. Seventeen patients developed significant common cold symptoms with increased nasal lavage fluid levels of alpha2-macroglobulin, IL-8, and ECP at baseline (p<0.001-0.05 versus before inoculation), and were further increased by allergen challenge (p< 0.001-0.05); IL-8 and ECP levels were correlated (r = 0.63, p<0.001). Before inoculation, the six patients who later did not develop common cold symptoms had high levels of IL-8 and myeloperoxidase (MPO), and exhibited strong allergen-induced plasma exudation responses (alpha2-macroglobulin). After inoculation, IL-8 and ECP did not increase in these symptomless subjects. In conclusion, high nasal interleukin-8 and myeloperoxidase levels and exudative hyperresponsiveness may protect against infection. The association between nasal interleukin-8 and eosinophil cationic protein in common cold, particularly that observed in nasal lavage fluids after allergen-induced acute exudation of plasma, suggests the involvement of interleukin-8 in exacerbation of airway mucosal eosinophil activity.

Adolescent↗
PubMed1999

Alpha2-macroglobulin and eosinophil cationic protein in the allergic airway mucosa in seasonal allergic rhinitis.

As previously demonstrated in seasonal allergic rhinitis, increased microvascular permeability and eosinophil activation are key features of allergic airway inflammation. In the present study, the hypothesis that exudation of alpha2-macroglobulin may cause the appearance of eosinophil cationic protein (ECP) in the airway lumen was explored. Nasal lavages were carried out using the nasal pool device before and during the pollen season both at baseline and after histamine challenge in 10 children with allergic rhinitis. Nasal lavage fluid levels of alpha2-macroglobulin and ECP were determined. All patients experienced nasal symptoms of allergic rhinitis during the pollen season (p<0.01-0.05). Baseline nasal lavage fluid levels of alpha2-macroglobulin and ECP were increased during the season (p<0.01-0.05) and were found to be well correlated (p<0.0001). Histamine produced concentration-dependent plasma exudation before and during the pollen season, but it was only during the pollen season that this caused an increase in the lavage fluid levels of ECP (p<0.05). These data suggest that exudation of plasma and increased tissue levels and output of eosinophil cationic protein characterize nasal mucosal inflammation in children with seasonal allergic rhinitis. The plasma exudation process in part may account for lumenal entry of eosinophil cationic protein molecules that have been released in mucosal tissue compartments. A combination of induced exudation and nasal lavage may improve the yield of important markers of inflammation in studies of nasal diseases.

Biomarkers↗
PubMed1998

Allergen challenge-induced extravasation of plasma in mouse airways.

BACKGROUND: Mouse models are extensively used to study genetic and immunological mechanisms of potential importance to inflammatory airway diseases, e.g. asthma. However, the airway pathophysiology in allergic mice has received less attention. For example, plasma extravasation and the ensuing tissue-deposition of plasma proteins, which is a hallmark of inflammation, has not been examined in allergic mice. OBJECTIVE: This study aims to examine the vascular permeability and the distribution of plasma proteins in mouse airways following exposure to allergen and serotonin. METHODS: Extravasated plasma was quantified by a dual isotop technique using intravascular (131I-albumin) and extrasvascular (125I-albumin) plasma tracers. Histological visualization of fibrinogen and colloidal gold revealed the tissue distribution of extravasated plasma. RESULTS: Allergen aerosol exposure (3% OVA, 15min) of sensitized animals resulted in a marked plasma extravasation response in the trachea (P < 0.01) and the bronchi but not in the lung parenchyma. A similar extravasation response was induced by serotonin (P<0.001). Extravasating vessels (assessed by Monastral blue dye) were identified as intercartilaginous venules. Extravasated plasma abounded in the subepithelial tissue but was absent in the epithelium and airway lumen. The allergen-induced response was dose-dependently inhibited by iv administration of formoterol (P < 0.001), a vascular antipermeability agent. CONCLUSION: The present study demonstrates that serotonin and allergen challenge of sensitized mice increase airway venular permeability to cause transient extravasation and lamina propria distribution of plasma in the large airways. We suggest that the extravasation response is a useful measure of the intensity and the distribution of active inflammation

Aerosols↗
PubMed1998

Contribution of plasma-derived molecules to mucosal immune defence, disease and repair in the airways.

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.

Absorption↗
PubMed1998

Generation of clusters of free eosinophil granules (Cfegs) in seasonal allergic rhinitis.

Generation of clusters of free eosinophil granules (Cfegs), through lysis of eosinophils, has recently been proposed as a major paradigm for ultimate activation of airway mucosal eosinophils. In the present study involving patients with seasonal allergic rhinitis, we have investigated whether generation of Cfegs in the nasal mucosa is a feature of allergic rhinitis. Nasal mucosal biopsies were obtained before and late in a birch-pollen season, and were subjected to histochemical staining of eosinophil peroxidase. In biopsies obtained before the pollen season, a few, intact eosinophils were observed, and Cfegs were scarce. In biopsies taken during the pollen season, the numbers of eosinophils were increased about 10-fold (P < 0.05) and the Cfegs about 25-fold (P < 0.05). We conclude that generation of Cfegs is a significant feature of seasonal allergic rhinitis and that this process represents the ultimate activation of mucosal eosinophils in this disease.

Biopsy↗