| 1. |
- Andersson, Anders, et al.
(författare)
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Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes
- 2004
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 138:1, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- CD4(+) and CD8(+) lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8(+) cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4(+) lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4(+) or CD8(+) lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2Ralpha) protein were also measured in conditioned medium from human blood CD4(+) and CD8(+) lymphocytes stimulated with tobacco smoke extract (TSE) in vitro. IL-16 mRNA was assessed in vitro as well, using reverse transcription-polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2Ralpha in conditioned medium from CD4(+) and CD8(+) lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8(+) cytokine IL-16, in the airway lumen, in blood CD4(+) and CD8(+) lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4(+) lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD.
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| 2. |
- Berg, L., et al.
(författare)
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LIR-1 expression on lymphocytes, and cytomegalovirus disease in lung-transplant recipients
- 2003
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Ingår i: Lancet. - 0140-6736. ; 361:9363, s. 1099-101
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Tidskriftsartikel (refereegranskat)abstract
- Human cytomegalovirus infection is a major cause of morbidity after lung transplantation. LIR-1 (leucocyte immunoglobulin-like receptor-1) is an inhibitory cell surface receptor that has high affinity for an MHC class I homologue (UL18) encoded by human cytomegalovirus. We aimed to investigate whether reactivation of human cytomegalovirus affects the expression of LIR-1. We measured LIR-1 expression on peripheral blood lymphocytes from 13 lung-transplant recipients and established human cytomegalovirus load using PCR. Eight patients developed cytomegalovirus disease. The percentage of cells expressing LIR-1 increased in the patients who developed cytomegalovirus disease several weeks before viral DNA was detectable by PCR. Measurement of LIR-1 expression might allow early identification of cytomegalovirus disease in lung-transplant patients.
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| 3. |
- Ericson, Petrea, 1966, et al.
(författare)
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BAL levels of interleukin-18 do not change before or during acute rejection in lungtransplant recipients
- 2004
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Ingår i: Respir Med. - : Elsevier BV. - 0954-6111. ; 98:2, s. 159-63
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVE: Acute rejection (AR) of the allograft is a major clinical problem after lungtransplantation. Repeated episodes of AR increase the risk of developing obliterative bronchiolitis, the main cause of mortality in this patient group. It is believed that AR is caused by T-lymphocytes reacting to donor antigens and in turn activating antigen presenting cells (APC) such as alveolar macrophages. Hypothetically, the interferon-gamma inducing cytokine IL-18 released from activated macrophages can play a role in the development of AR by modulating cytotoxic T-lymphocytes. DESIGN: To determine whether IL-18 may serve as a marker of AR, we retrospectively analysed the concentration of soluble IL-18 protein and inflammatory cells in bronchoalveolar lavage fluid (BAL) from lungtransplant recipients. PATIENTS: To minimize confounding factors, eight pairs of patients were matched for age, gender, pre-op diagnosis, type of operation, absence of infection and time post transplant. METHODS: BAL levels of IL-18 (ELISA) and BAL cell differentials were analysed before, during and after an episode of AR and compared with the matched control group. CONCLUSION: We found no changes in IL-18 concentration in BAL associated with AR. IL-18 in BAL did not correlate with BAL lymphocyte percentage. We conclude that change in soluble IL-18 protein does not constitute a useful marker of acute rejection in lung allograft recipients.
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| 4. |
- Kjellström, Christer, 1955, et al.
(författare)
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The origin of alveolar macrophages in the transplanted lung: a longitudinal microsatellite-based study of donor and recipient DNA
- 2000
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Ingår i: Transplantation. - 0041-1337. ; 69:9, s. 1984-6
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Tidskriftsartikel (refereegranskat)abstract
- Transplanted lungs are initially populated by donor pulmonary alveolar macrophages (PAMs). These will form major antigen presenters for the recipient's suppressed immune system. They may be expected to be replaced by recipient major histocompatibility complex-compatible cells, with time. We have isolated CD14+ PAMs from bronchoalveolar lavage specimens for 6 months after transplantation and identified their origin by using microsatellite analysis. This DNA-based technology permits the reliable identification of the origin of cells from different individuals. We show that replacement of donor PAMs occurs with individual dynamics in each case. Recipient PAMs usually appeared within 2 weeks, whereas donor cells could be retained for as long as 6 months. In this limited series, there was no obvious correlation between the dynamics of this process and the occurrence of rejection episodes or infections.
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| 5. |
- Laan, Martti, 1971, et al.
(författare)
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IL-16 in the airways of lung allograft recipients with acute rejection or obliterative bronchiolitis
- 2003
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Ingår i: Clin Exp Immunol. - 0009-9104. ; 133:2, s. 290-6
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Tidskriftsartikel (refereegranskat)abstract
- Acute rejection (AR) is the principal risk factor for obliterative bronchiolitis (OB), the major complication of lung transplantation. It is known that activated CD4+ T lymphocytes are involved in the development of AR and that interleukin (IL)-16 can inhibit the activity of CD4+ T lymphocytes. In this study, we evaluated whether the concentration of IL-16 in the airways is altered in AR or OB and, if so, how this IL-16 concentration relates to the number or activity of airway lymphocytes. The concentration of IL-16 protein was measured in bronchoalveolar lavage (BAL) fluid at three time-points in lung allograft recipients with either AR or OB and in matched controls using ELISA. The concentration of soluble IL-2 receptor (R) protein was measured in BAL fluid using ELISA as well, as an indicator of lymphocyte activity. The percentage of airway lymphocytes was evaluated by performing BAL differential cell counts. Lung allograft recipients with AR displayed lower IL-16 concentrations compared with matched control patients and this IL-16 concentration correlated negatively with the sIL-2R concentration, but it did not correlate with the percentage of lymphocytes in BAL fluid. In contrast, in BAL fluid from lung allograft recipients with OB, the IL-16 concentration was not altered compared with matched control patients and it did not correlate with the percentage of lymphocytes or with the sIL-2R concentration. These data are compatible with an increase in IL-16 playing a protective role against AR but not against OB and, hypothetically, this type of protective effect could be exerted via a down-regulation of the activity of T lymphocytes.
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| 6. |
- Nord, M., et al.
(författare)
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Decreased serum and bronchoalveolar lavage levels of Clara cell secretory protein (CC16) is associated with bronchiolitis obliterans syndrome and airway neutrophilia in lung transplant recipients
- 2002
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 73:8, s. 1264-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The major hinderance for long-term survival after lung transplantation is chronic rejection in the form of bronchiolitis obliterans syndrome (BOS). BOS is a fibrosing process in the small airways causing irreversible airway obstruction. BOS is associated with increased oxidative burden and activation of inflammatory and growth-stimulating mediators. The Clara cell secretory protein (CCSP or CC16) is a secreted differentiation marker for the bronchiolar epithelium with both antioxidative and antiinflammatory/immmunomodulatory properties. We asked whether this molecule could have a role in the development of BOS. METHODS: Serum and bronchoalveolar lavage (BAL) fluid samples were collected from 22 consecutive lung transplant recipients, the majority (19) was followed for 2 years. Six patients developed BOS. CCSP in serum was measured in 162 samples from 19 patients with an ELISA method, and CCSP in 191 BAL samples from 22 patients with quantitative Western blot. RESULTS: CCSP in both serum and BAL was significantly lower in BOS compared with acute rejection or no rejection. After the first postoperative month, serum and BAL CCSP levels were consistently lower in the patients who developed BOS than in those who did not. The percentage of neutrophils in BAL correlated negatively with CCSP in BAL. CONCLUSIONS: Levels of CCSP in serum and BAL is lowered in BOS. Serum CCSP could have a potential as an early marker for BOS. The correlation between decreased CCSP and increased neutrophils in BAL suggests a loss of local airway defense capacity in BOS.
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| 7. |
- Qvarfordt, Ingemar, 1954, et al.
(författare)
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IgG subclasses in smokers with chronic bronchitis and recurrent exacerbations
- 2001
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Ingår i: Thorax. - 0040-6376. ; 56:6, s. 445-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tobacco smokers have lower serum levels of IgG than non-smokers. IgG subclass deficiency is common in patients with recurrent respiratory infections. Recurrent bronchial infections are common in smokers with chronic bronchitis (CB). We have investigated whether susceptibility to recurrent exacerbations in smokers with CB is associated with altered IgG subclass levels or IgG subclass deficiency. METHODS: Serum levels of IgG, IgA, IgM, and IgG subclasses 1-4 were determined by radial immunodiffusion in 100 subjects: 33 smokers with stable CB and recurrent exacerbations, 24 asymptomatic smokers, and 43 healthy never smokers. Systemic tobacco exposure was verified and excluded using a serum cotinine ELISA. Immunoglobulin data were log transformed to enable use of parametric statistical methods. RESULTS: Compared with never smokers, both patients with CB and asymptomatic smokers had significantly lower levels of IgG (median 9.7 g/l (range 5.6-15.2) and 9.9 (6.1-12.1) g/l v 12.0 (6.9-18.5) g/l) and IgG2 (2.8 (0.9-5.9) g/l and 2.5 (1.0-6.3) g/l v 4.0 (1.7-10.2) g/l). The estimated ratio of median values between the patients with CB and never smokers was 0.78 (95% confidence interval (CI) 0.69 to 0.89) for IgG and 0.65 (95% CI 0.50 to 0.83) for IgG2. The corresponding ratios between asymptomatic smokers and never smokers were 0.79 (95% CI 0.69 to 0.91) and 0.60 (95% CI 0.50 to 0.83), respectively. There were no significant differences between the smoking groups. CONCLUSIONS: Susceptibility to recurrent exacerbations in smokers with CB is not associated with lower levels of IgG subclasses than can be accounted for by smoking per se.
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| 8. |
- Qvarfordt, Ingemar, 1954, et al.
(författare)
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Lower airway bacterial colonization in asymptomatic smokers and smokers with chronic bronchitis and recurrent exacerbations
- 2000
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Ingår i: Respir Med. - 0954-6111. ; 94:9, s. 881-7
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial colonization of the lower airways in patients with chronic bronchitis (CB) has been described mainly in patients with co-existing chronic obstructive pulmonary disease (COPD). Although smoking has been identified as a risk factor for bacterial colonization it is not known whether asymptomatic smokers (AS) can be colonized. The aim of this study was to study lower airway bacterial colonization in smokers with stable CB and recurrent exacerbations and compare with AS and healthy never-smokers (NS). Thirty-nine smokers with CB and recurrent exacerbations (median FEV1 85% of predicted normal), 10 AS and 10 NS, underwent bronchoscopy and a two-step bronchoalveolar lavage (BAL) procedure where the first portion (20 ml, 'pre-BAL') was recovered separately from the rest (140 ml, 'BAL'). The degree of oropharyngeal contamination of pre-BAL and BAL samples was evaluated by cytology. Semiquantitative bacterial cultures were performed on all samples. Higher bacterial numbers than 10(3) colony-forming units (cfu) x ml(-1) in BAL were found only in the two smoking groups. Using 10(3) cfu x ml(-1) as cut-off, 6/10 (60%) in the AS-, and 7/35 (20%) in the CB-group were colonized in the lower airways. In all, 29% of all smokers had bacterial colonization. Only bacteria belonging to the normal oropharyngeal flora were found. The proportion of samples with oropharyngeal contamination was significantly lower in BAL than in pre-BAL (5% vs. 21%, P=0.039). The proportion of sterile samples was significantly higher in BAL than in pre-BAL (49% vs. 26%, P=0.002). Lower airway bacterial colonization was found both in asymptomatic smokers and in patients with CB. Colonization with potential respiratory pathogens is uncommon in patients with CB and recurrent exacerbations without severe airflow obstruction. The two-step BAL procedure seems to decrease oropharyngeal contamination.
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| 9. |
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| 10. |
- Riise, Gerdt C., 1956, et al.
(författare)
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Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro
- 2000
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Ingår i: Respiration. - 0025-7931. ; 67:5, s. 552-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bacterial adherence to mucosal and epithelial cell structures is of importance for the persistence of bacteria in the airways. Cigarette smoking and chronic bronchitis are associated with increased bacterial adherence. N-Acetylcysteine (NAC) medication reduces the number of infectious exacerbations in patients with chronic bronchitis, and NAC medication has been associated with low intrabronchial bacterial numbers. OBJECTIVE: We investigated whether NAC influences bacterial adherence as a possible mechanism behind its clinical effects. METHODS: Highly adhering test strains of Streptococcus pneumoniae and Haemophilus influenzae were used to investigate the influence of four pharmacological compounds on adherence to oropharyngeal epithelial cells in vitro. Adhesion assays were performed both during short-term exposure to, as well as after long-time incubation with, NAC, lidocaine, hydrocortisone and terbutaline at concentrations not inhibiting bacterial growth. RESULTS: Only NAC showed a significant inhibitory effect on adhesion of H. influenzae during short-term incubation. After long-term incubation, both NAC and hydrocortisone inhibited bacterial adhesion for both strains in a dose-dependent manner. When NAC's effect on three different strains of S. pneumoniae and four strains of H. influenzae was studied, inhibition of bacterial adhesion was found for three strains of each species. CONCLUSIONS: NAC lowers bacterial adhesion in vitro to oropharyngeal epithelial cells in doses equivalent to that is being used clinically. This effect might be a contributory mechanism behind the reduction of infectious exacerbations in chronic bronchitis patients.
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| 11. |
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| 12. |
- Riise, Gerdt C., 1956, et al.
(författare)
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Quantification of cytomegalovirus DNA in BAL fluid: a longitudinal study in lung transplant recipients
- 2000
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Ingår i: Chest. - 0012-3692. ; 118:6, s. 1653-60
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVES: Cytomegalovirus (CMV) infection is common in patients receiving solid organ transplants, and it is associated with increased morbidity as well as risk for development of chronic rejection. A rapid and sensitive diagnostic method would improve the therapeutic management of CMV infection, including the monitoring of treatment effects. We investigated whether longitudinal determinations of CMV DNA quantities in BAL fluid could be useful for this purpose. DESIGN: CMV DNA levels in 340 BAL samples from 35 consecutive lung transplant recipients were studied during a median of 18 months. Seventeen (49%) of the patients developed CMV disease with pneumonitis. Twenty-seven CMV disease episodes were diagnosed. RESULTS: Patients with CMV disease had a significantly higher mean level of CMV copies per milliliter BAL fluid (1,120 +/- 4,379) compared with those without (180 +/- 1,177, p < 0.01). Viral load as well as acute rejection requiring treatment (>/= A2) were independent risk factors associated with CMV disease. Differences between the groups concerning HLA-DR matching, basic immunosuppressive therapy, and CMV serologic status D/R -/+ vs D/R +/+ were not significant. A diagnostic definition of normality based on the mean level of all episodes without CMV disease +2 SD would discriminate only 9 of the 27 CMV episodes. CONCLUSIONS: Although the viral load is increased during episodes of clinical CMV disease in lung transplant recipients, the quantitative PCR assessment of CMV DNA in BAL fluid is not discriminative enough to be useful as a diagnostic tool for CMV disease.
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| 13. |
- Seymour, M. L., et al.
(författare)
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Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics
- 2001
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Ingår i: Am J Respir Crit Care Med. - 1073-449X. ; 164:11, s. 2051-6
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Tidskriftsartikel (refereegranskat)abstract
- Cysteinyl-leukotrienes and prostaglandin D2 generated by the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways, respectively, cause bronchoconstriction, leukocyte recruitment, and bronchial hyperresponsiveness in asthma. We characterized the cellular expression of 5-LO and COX enzymes using immunohistochemistry on bronchial biopsies from 12 allergic asthmatic patients before and during seasonal exposure to birch pollen. Bronchial responsiveness (p = 0.004) and symptoms (p < 0.005) increased and peak expiratory flow (PEF; p < or = 0.02) decreased in the pollen season. In-season biopsies had 2-fold more cells immunostaining for 5-LO (p = 0.02), 5-LO-activating protein (FLAP; p = 0.04), and leukotriene (LT)A4 hydrolase (p = 0.05), and 4-fold more for the terminal enzyme for cysteinyl-leukotriene synthesis, LTC4 synthase (p = 0.02). Immunostaining for COX-1, COX-2, and PGD2 synthase was unchanged. Increased staining for LTC4 synthase was due to increased eosinophils (p = 0.035) and an increased proportion of eosinophils expressing the enzyme (p = 0.047). Macrophages also increased (p = 0.019), but mast cells and T-lymphocyte subsets were unchanged. Inverse correlations between PEF and 5-LO(+) cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure.
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| 14. |
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