PubMed Health⌕ Search

Biomedical subjects

L O Cardell

Publications and source records attributed to L O Cardell.

At least 19 recordsLinked to original sources
PubMed2005

Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis.

BACKGROUND: Intermittent allergic rhinitis (IAR) results from interactions between a large number of pro- and anti-inflammatory mediators. Little is known about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous analysis of the whole transcriptome in a sample. OBJECTIVE: To identify anti-inflammatory transcripts in nasal fluid cells from patients with IAR during season and from healthy controls. METHODS: Nasal lavage fluids were obtained from 15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy controls. RNA was extracted from the nasal fluid cells and pooled into one patient- and one control pool. These were analysed with DNA microarrays containing more than 44,927 genes and variants. RESULTS: Seventeen thousand three hundred and fifty three genes were expressed in the controls and 17 928 in the patients. One thousand five hundred and seventy nine of the genes had higher expression in patients than in controls, and 1570 had lower expression in patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory and two were anti-inflammatory. These genes regulated key steps of inflammation, ranging from influx of leukocytes to immunoglobulin production. By comparison, out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were anti-inflammatory. The anti-inflammatory gene that decreased most in expression in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The nasal fluid concentrations of uteroglobin protein were significantly lower in patients than in controls, 5.43+/-1.53 and 12.93+/-2.53 ng/mL, respectively (P<0.05). CONCLUSION: IAR is associated with decreased expression of uteroglobin and other anti-inflammatory genes.

Adolescent↗
PubMed2004

Intranasal steroids decrease eosinophils but not mucin expression in nasal polyps.

Increased mucin expression is a feature of nasal polyposis. Corticosteroids reduce polyp size and symptoms, but their effect on mucin production remains unknown. In this study, the effects of intranasal corticosteroids on MUC5AC mucin expression, nasal resistance, eosinophil and neutrophil infiltration, epidermal growth factor receptor (EGFR), interleukin (IL)-8, and tumour necrosis factor (TNF)-alpha expression was assessed in nasal polyps. In nine subjects, one nasal polyp was removed surgically before treatment and another was removed after 8 weeks of intranasal fluticasone (400 microg.day(-1)). Tissues were processed for in situ hybridisation and immunohistochemical staining. Described effects of fluticasone on nasal polyps (reduction in nasal resistance and in eosinophil infiltration) were evaluated. Morphometric analysis was performed to assess the effect of fluticasone on epithelial-, MUC5AC-, EGFR- and IL-8-stained areas, TNF-alpha-stained cells, and neutrophil numbers. Treatment with fluticasone decreased nasal resistance and intra-epithelial eosinophils. The MUC5AC-stained area in the epithelium was unchanged by treatment; MUC5AC mRNA expression was unaffected by treatment. EGFR-stained area, intra-epithelial neutrophil numbers, IL-8 and TNF-alpha expression were also unchanged by therapy. Intranasal fluticasone was effective in decreasing nasal airflow resistance and intra-epithelial eosinophils but had no effect on mucin or epidermal growth factor receptor expression or on neutrophil recruitment.

Administration, Intranasal↗
PubMed2003

Allergen-reactive antibodies are found in nasal fluids from patients with birch pollen-induced intermittent allergic rhinitis, but not in healthy controls.

BACKGROUND: Increased levels of allergen-reactive immunoglobulins (Igs) have been reported in nasal fluids from patients with intermittent allergic rhinitis (IAR) sensitive to ragweed and grass. The aims of this study were to make a detailed characterization of nasal fluid Igs in birch pollen-induced IAR. METHODS: Nasal fluids were obtained from 23 patients with birch pollen-induced IAR during and after the birch pollen season, and from 20 healthy controls. Nasal fluid total and Bet v 1-reactive (IgA), IgE and IgG as well as albumin were analyzed by immunoassays. The integrity of IgA and IgG, and the molecular form of IgA were assessed by Western blotting and column fractionation, respectively. RESULTS: Nasal fluid total IgE and IgG, but not IgA, were higher in patients compared with controls. Western blotting indicated no significant degradation of IgA (including S-IgA) and IgG. Most of the IgA, including Bet v 1-reactive antibodies, was of the secretory form and of the IgA1 subclass. Bet v 1-reactive IgA and IgG were present in all patients, but was mostly nondetectable in controls. No significant differences in the levels of Bet v 1-reactive IgA and IgG were found in patients during the birch pollen season compared with off season. Both Bet v 1 and Bet v 2-reactive IgE were nondetectable in most samples. CONCLUSIONS: Nasal fluid Bet v 1-reactive IgA and IgG were found in all patients with birch pollen-induced IAR, but not in controls. However, no significant differences were found between patients during and after the birch pollen season.

Adolescent↗
PubMed2003

Increased expression of surface activation markers on neutrophils following migration into the nasal lumen.

BACKGROUND: The sequence of events following the recruitment of a free-flowing neutrophil in the peripheral circulation, via adhesion, migration and release of mediators, to a neutrophil on the surface of the nasal epithelium is a co-ordinated process. Little is known about the state of neutrophil activation following this course of events. OBJECTIVES: To investigate the expression of surface activation markers on neutrophils, reflecting activation during their recruitment to the nose, and to see whether the inflammatory process during allergic rhinitis influences this process. METHOD: Nine healthy controls and 12 patients with grass pollen-induced intermittent allergic rhinitis were investigated during the peak of the pollen season. The expression of CD11b, CD66b and CD63 on the neutrophil cell surface, as a reflection of activation, was analysed using flow cytometry. Neutrophils were derived from peripheral blood and nasal lavage fluid. In addition, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) as well as L-, P- and E-selectins in the nasal lavage fluid were analysed using RIA and ELISA, respectively. RESULTS: A marked increase in the expression of all three CD markers on the neutrophil cell surface was noticed following migration from the bloodstream to the surface of the nasal mucosa. At the peak of the grass pollen season, the MPO levels increased, reflecting an increase in the total number of nasal fluid neutrophils. In parallel, the expression of CD11b was further augmented. The expression of the CDb11b was reduced on neutrophils remaining in the circulation. In addition, the level of L-selectin was reduced on neutrophils derived from the blood during allergic inflammation. CONCLUSION: Neutrophils might become activated during their transfer from the blood to the surface of the nasal mucosa, but these changes may also be due to depletion of activated neutrophils in the blood via activated endothelial/epithelial adhesion and chemoattractant measures. The increased expression of surface activation markers during allergic rhinitis suggests roles for neutrophils in the inflammatory process.

Adult↗
PubMed2003

Pituitary adenylate cyclase-activating polypeptide, effects in the human nose.

BACKGROUND: Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide with strong vaso- and bronchodilator capacity. There is recent evidence that PACAP decreases the release of proinflammatory cytokines and we have previously shown that PACAP inhibits neutrophil chemotaxis in vitro, but little is known about the effects of PACAP in human upper and lower airways. OBJECTIVE: To investigate the effects of PACAP in the human upper respiratory tract focusing on vasodilatation/nasal airway resistance (NAR), neutrophil recruitment, plasma extravasation and endogenous production of IL-1-related mediators. METHODS: Surgical specimens from five patients (aged 19-55 years), obtained in conjunction with nasal surgery, were used for immunohistochemical localization of PACAP in the nasal mucosa. In seven, healthy, non-allergic, non-smoking subjects (aged 19-45 years), NAR was measured with rhinomanometry. Nasal lavage was performed, before and after intranasal application of PACAP (200 microL of a 1 microm PACAP solution in each nasal cavity), with and without the addition of histamine. Cells, albumin and IL-1-related mediators were analysed in nasal lavage. In addition, the effects on pulse, blood pressure, ECG and pulmonary function were evaluated. RESULTS: In the nasal mucosa, PACAP-like immunoreactive nerve fibres were seen close to blood vessels and seromucous glands. Application of PACAP in the nasal cavity increased NAR and augmented the increase in NAR induced by histamine. In addition, PACAP inhibited histamine-induced recruitment of neutrophils, increased plasma leakage and reduced the level of IL-1RA (an endogenously produced IL-1 receptor antagonist) in nasal lavage. Cardiovascular and pulmonary parameters were not affected. CONCLUSION: These results imply that PACAP is an important endogenous mediator in human upper airways, with a potential role as a regulator of vascular smooth muscle, secretion, plasma extravasation, neutrophil recruitment and cytokine activity.

Adult↗
PubMed2002

Hemin, a heme oxygenase substrate analog, inhibits the cell surface expression of CD11b and CD66b on human neutrophils.

BACKGROUND: Neutrophils are signaled to sites of infection and inflammation by different chemotactic stimuli. In order to reach the airways they have to adhere to, and then migrate through, the endothelium of pulmonary vessels. Carbon monoxide (CO) is a gaseous mediator, endogenously produced in the human airways. Increased CO production has been demonstrated during airway inflammation and CO as well as hemin, a substrate for CO producing enzymes, has been shown to affect neutrophil migration. Our objective was to investigate if the neutrophil cell surface expression of CD11b, CD66b and CD63 was changed during intermittent allergic rhinitis and to establish whether CO could affect the expression of these markers of cellular activation. METHODS: Blood from 10 healthy volunteers was drawn and incubated with different concentrations of hemin. Blood from 12 other healthy volunteers and from 12 patients with intermittent allergic rhinitis was also drawn during grass pollen season. Neutrophils were then isolated from all these three sets, and their expression of CD antigens measured using flow cytometry. RESULTS: Patients with symptomatic intermittent allergic rhinitis exhibited lower levels of CD11b and CD66b on the neutrophil cell surface. Incubation with hemin decreased the expression of CD11b and CD66b. CD63 was generally weakly expressed and not significantly affected by hemin incubation. CONCLUSION: Our results demonstrate that expressions of neutrophil cell surface glycoproteins are changed during the season in patents with intermittent allergic rhinitis and that hemin, a substrate for CO production, may act as an inhibitor of neutrophil activation. This indicates a possible role for CO in the immune defense system.

Antigens, CD↗
PubMed2002

DNA microarrays to study gene expression in allergic airways.

BACKGROUND: Allergic rhinitis results from interactions between a large number of cells and mediators in different compartments of the body. DNA microarrays allow simultaneous measurement of expression of thousands of genes in the same tissue sample. OBJECTIVE: To study gene expression in nasal mucosal biopsies from patients with allergic rhinitis using DNA micro-arrays. METHODS: Nasal biopsies were obtained from 14 patients with symptomatic birch pollen-induced allergic rhinitis and five healthy controls. RNA was extracted from the biopsies and pooled into one patient pool and one control pool. These were analysed in duplicate with DNA micro-arrays containing more than 12 000 known genes. RESULTS: Approximately half of the genes were expressed in the patient and control samples. Guided by the current literature we chose 32 genes of possible relevance to allergic airway inflammation and investigated their relative expression. Among these, transcripts encoding immunoglobulins and their receptors were most abundant. The expression of cytokines and growth factors was low, whereas their corresponding receptors and cell surface markers displayed higher expression levels. IgA had the highest expression of all 12 626 genes. RT-PCR showed that IgA1 was the predominant subclass. This was confirmed by the protein level in nasal fluids. Allergen-specific IgA was significantly higher in patients than in controls and correlated significantly with eosinophil granulae proteins. CONCLUSION: DNA micro-array analysis can be used to identify genes of possible relevance to allergic airway inflammation. In this study, the expression profile in the nasal mucosa was quantitatively dominated by immunoglobulins, particularly IgA. Protein analyses in nasal fluids indicated a role for allergen-specific IgA in eosinophil degranulation.

Adult↗
PubMed2001

The induction of carbon monoxide-mediated airway relaxation by PACAP 38 in isolated guinea pig airways.

Pituitary adenylate cyclase--activating peptide 38 (PACAP 38) displays several biologic activities relevant to obstructive airway disease. Carbon monoxide (CO) has recently emerged as a potent, endogenously produced mediator of bronchodilation. In this study, we have analyzed the occurrence of PACAP 38 and the corresponding occurrence of heme oxygenase (HO), the rate-limiting enzyme for CO production, in guinea pig trachea, using immunocytochemistry. We have also investigated whether the dilatory effects of PACAP 38 are dependent on CO, using an in vitro setup for tracheal studies. A moderate supply of PACAP-like immunoreactive nerve fibers was seen in association with tracheal smooth muscle. HO-like immunoreactivity was observed in the respiratory epithelium and in association with smooth muscle bundles. PACAP 38 induced a concentration-dependent relaxation of precontracted tracheal segments. This dilation was nearly abolished after pretreatment with zincprotoporphyrine, an inhibitor of heme oxygenase. The same effect was accomplished with Rp-8Br-cyclicGMPS, an inhibitor of cyclicGMP, whereas the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine had no effect on the PACAP 38--induced dilation. The presented data suggest that PACAP 38 can induce bronchodilation by means of a CO-dependent, cyclicGMP-related mechanism, thereby providing a link between neurotransmission and local CO release in the airway smooth muscle.

Animals↗
PubMed2001

Helospectin, induces a potent relaxation of human airways in vitro.

Helospectin is a neuropeptide of the vasoactive intestinal polypeptide/secretin/glucagon family. Several members of this family display biological activities relevant to obstructive airway disease and although the literature in this area is rapidly expanding very little is known about the effects of helospectin. The smooth muscle relaxation induced by helospectin on human bronchi and pulmonary arteries were therefore assessed in vitro, using tissue baths. Helospectin induced a potent relaxation of human bronchi and since helospectin-like immunoreactive nerve fibers along with possible target receptors previously have been reported in the human lung, helospectin might play a role in endogenous regulation of airway tone.

Acetylcholine↗
PubMed2001

Pituitary adenylate cyclase-activating peptide inhibits neutrophil chemotaxis.

Pituitary adenylate cyclase-activating peptide 38 (PACAP 38) is a neuropeptide that displays several biological effects of interest in the context of airway diseases such as asthma and chronic obstructive pulmonary disease. These effects include inhibition of airway and vascular smooth muscle tone as well as modulation of inflammatory cell activity. However, little is known about the effect of PACAP on granulocytes. The present study was designed to investigate if PACAP and the closely related peptide vasoactive intestinal peptide (VIP) could affect neutrophil migration. A standard 48 well chemotaxis chamber was used to assess the effects of PACAP on N-Formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced neutrophil chemotaxis and spontaneous random migration. PACAP 38 and VIP inhibited fMLP-induced human neutrophil chemotaxis. Furthermore, both peptides also exhibited a dose-related trend toward inhibiting the spontaneous, unstimulated migration of neutrophils. Since enhanced cell migration in cell chamber systems is reported to correlate with increased invasive properties in vivo, the presented inhibitory effects of PACAP 38 on neutrophil chemotaxis, supports the idea of an anti-inflammatory role for PACAP. This together with the well documented bronchodilatory capacity of PACAP might indicate a role for PACAP-agonists in future treatment of asthma and other inflammatory airway diseases.

Chemotaxis, Leukocyte↗
PubMed2001

Expression of 5-HT1B receptors in human nasal mucosa.

5-HT1B receptors were discovered in human nasal mucosa using immunocytochemistry. Strong immunoreaction was seen around small blood vessels mainly confined to the smooth muscle cell layer. In contrast, no immunoreaction for 5-HT1D was seen. The possibility of local release in connection with specific target receptors suggests a role for 5-HT in the regulation of vascular tone, glandular secretion and epithelial functions and that 5-HT1B receptor agonists may be of clinical importance.

Adult↗
PubMed2000

Carbon monoxide is endogenously produced in the human nose and paranasal sinuses.

BACKGROUND: Carbon monoxide (CO) has recently emerged as an endogenously produced gaseous mediator that, like nitric oxide (NO), appears to be involved in both upper and lower airway inflammation. In healthy subjects a large part of the exhaled NO seems to originate from the nasal airways, and the paranasal sinuses have been described as a dominating site for NO production. OBJECTIVE: The current study was designed to investigate whether CO could also be produced in the nose and paranasal sinuses. METHODS: The occurrence in the nasal mucosa of the enzyme heme oxygenase, the rate limiting step for CO production, was analyzed with use of immunocytochemistry. CO in exhaled and sampled air was measured with an infrared analyzer. Forty-two healthy subjects and two patients with a tracheostoma volunteered for the study. RESULTS: Heme oxygenase-like immunoreactivity was seen in the respiratory epithelium, in connection with seromucous glands and in the vascular smooth muscle of the nose. When CO was continuously sampled from one nostril during normal breathing through the mouth, stable levels of CO could be measured within 40 seconds in all subjects tested (n = 33). Repeated measurements indicated only minor variations in the values obtained. Sampling through a drainage tube inserted into the maxillary sinus revealed CO levels comparable to the levels obtained by sampling through the nose (n = 6). Breathing through the nose increased the CO levels obtained in the exhaled air (n = 33, P <. 001). CONCLUSION: These results imply that the nose and paranasal sinuses contribute to the CO production of the human airways.

Adult↗
PubMed2000

Pituitary adenylate cyclase-activating peptide 38 a potent endogenously produced dilator of human airways.

Pituitary adenylate cyclase-activating peptide (PACAP) 38 displays several biological activities relevant to obstructive airway disease. In this study, the occurrence of PACAP 38 in human small bronchi and corresponding pulmonary arteries was analysed immunocytochemically. The dilatory effects of this peptide on the same structures were also studied in vitro. A moderate number of PACAP-like immunoreactive nerve fibres was seen in association with bronchial and vascular smooth muscle and around seromucous glands. PACAP 38 caused a concentration-dependent relaxation of precontracted bronchial and pulmonary arterial segments. The maximal relaxation was more pronounced in the airways than in the arteries, whereas the potency in both was identical. PACAP 38 caused relaxation of all segments tested (nine patients), whereas vasoactive intestinal polypeptide (VIP) failed to cause relaxation of bronchial segments from six of nine patients. Both PACAP and VIP dilated all pulmonary arterial segments tested. In conclusion, pituitary adenylate cyclase-activating peptide 38 is a potent dilator of human bronchi and is present in the human lung. Pituitary adenylate cyclase-activating peptide 38 may, therefore, play a role in the endogenous regulation of airway tone. The inhibitory effects of pituitary adenylate cyclase-activating peptide 38 are more consistent than those of the related neuropeptide vasoactive intestinal polypeptide, perhaps reflecting a difference in susceptibility to degrading enzymes.

Aged↗
PubMed2000

Nitric oxide-dependent neutrophil recruitment: role in nasal secretion.

Leukotriene B4 (LTB4), an inflammatory mediator, is a potent chemoattractant for neutrophils that plays an important role in nasal secretion via release of elastase. Nitric oxide (NO) is an important modulator of leucocyte-endothelial cell interactions, endogenously produced in large quantities in the paranasal sinuses. To examine the role of NO in LTB4-stimulated nasal secretion. A newly-developed method for isolating and superfusing a nasal segment in dogs was used. Instillation of LTB4 into the nasal segment caused a time-dependent increase in the volume of airway fluid and in the recruitment of neutrophils. N(G)-nitro-L-arginine-methylester (L-NAME), an inhibitor of NO synthase, prevented LTB4-induced neutrophil recruitment and nasal secretion. These studies show that NO modulates LTB4-induced neutrophil recruitment and subsequent fluid secretion in the nose, and they suggest a therapeutic role for NO inhibitors in modulating neutrophil-dependent nasal secretion.

Animals↗
PubMed2000

Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during grass pollen season: effect of a local glucocorticoid.

BACKGROUND: Allergic rhinitis is a common disease characterized by infiltration of eosinophils into the nasal mucosa during the periods of symptoms. Among chemokines, which attract cells to the site of inflammation, eotaxin is relatively specific for eosinophils. OBJECTIVE: We examined the influence of grass pollen season on nasal eotaxin expression in patients with seasonal allergic rhinitis, as well as the effect of a nasal glucocorticoid on this eotaxin expression. METHODS: Nineteen patients with allergic rhinitis received treatment with either nasal beclomethasone (400 microgram/day) or placebo over a grass pollen season. In these patients, nasal biopsies were taken prior to and during the peak of the pollen season and stained immunohistochemically for eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave nasal biopsies once prior to the pollen season. RESULTS: Prior to pollen season, there was no significant difference in nasal eotaxin expression between patients with allergic rhinitis and healthy subjects. Grass pollen season induced significant increase in eotaxin expression in placebo-treated (P = 0.04; n = 9) but not in beclomethasone-treated rhinitis patients (P = 0.8; n = 10). During peak grass pollen season, the eotaxin expression in placebo-treated patients was significantly higher compared with healthy subjects outside season (P = 0.03). There was no significant correlation between the expression of eotaxin and the number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in rhinitis patients remained stable over the pollen season. CONCLUSION: Expression of eotaxin in nasal mucosa of grass-pollen allergic rhinitis patients is upregulated during pollen season and treatment with a nasal glucocorticoid protects against this upregulation.

Administration, Topical↗
PubMed2000

Nasal secretion in ragweed-sensitized dogs: effect of leukotriene synthesis inhibition.

Allergic rhinitis is an inflammatory disease associated with local leukotriene release during periods of symptoms. Zileuton, a leukotriene synthesis inhibitor, is known to inhibit the release of leukotriene B4. Because we previously showed that leukotriene B4 is a potent mediator of neutrophil-dependent nasal secretion, we investigated whether Zileuton inhibited allergen-induced nasal secretion. Using a newly developed method for isolating and superfusing a nasal segment, we examined the effect of Zileuton on nasal secretion and neutrophil recruitment in ragweed-sensitized dogs. Instillation of ragweed into the nasal segment caused time-dependent increases in the volume of airway fluid and the recruitment of neutrophils. Zileuton prevented ragweed-induced neutrophil recruitment and nasal secretion. These results indicate that leukotrienes are important mediators of allergy-induced nasal secretion in dogs. Future clinical studies in allergic patients will determine whether there is a therapeutic role for leukotriene synthesis inhibitors in modulating neutrophil recruitment and hypersecretion in the nose.

Animals↗