Segmental Allergen Provocation Research Articles

Isolated aggregates of lymphoid cells in the inner bronchial wall in asthma patients.

Here, we report findings in volunteers with bronchial asthma. Biopsies were obtained from the inner bronchial wall before and a short time again after segmental allergen provocation. In most of the baseline biopsies and in all evaluable biopsies after segmental allergen provocation, the follicular lymphoid tissue was detected by immunohistochemistry in the epithelium of these asthmatic patients. The basic occurrence of the tertiary lymphoid tissue in the bronchial mucosa of mild asthmatics was unexpected and may have consequences for the interpretation of pathophysiology, e.g., as a cause or consequence of bronchial asthma.

Biphasic activation of complement and fibrinolysis during the human nasal allergic response

Biphasic activation of complement and fibrinolysis during the human nasal allergic response

Phase-contrast MRI for Detection of Mild Systemic Hemodynamic Response after Segmental Allergen Challenge in Asthmatic Patients

Detection of a systemic hemodynamic response in patients suffering from allergic asthma after segmental endobronchial allergen challenge using phase-contrast magnetic resonance imaging (MRI). Nine asthma patients and four healthy volunteers were examined using MRI (1.5T) before (0 hour), 6 hours, and 24 hours after segmental allergen challenge. Two-dimensional phase-contrast MRI measurements were performed in the aorta (AO) and in the pulmonary artery (PA). In addition, short-axis balanced steady state free precession cardiac cine MRI was performed. Maximum systolic flow, maximum flow acceleration, acceleration volume, acceleration time, distensibility, ejection fraction, stroke volume, end-systolic/diastolic volume, cardiac mass, heart rate (HR), and cardiac output (CO) were determined. Spirometry and bronchoalveolar lavage were also performed. In patients with asthma, maximal systolic flow and maximal flow acceleration increased 6 hours after provocation in the AO (112.3% and 118.9%, respectively) and PA (113.9% and 116.0%, respectively) compared to baseline (100%, P<.05). HR and CO increased significantly at 6 hours (115% and 118%, respectively) compared to baseline (100%, P=.003). In healthy subjects, almost all MRI-derived hemodynamic parameters did not significantly change at 6 hours and were significantly lower than baseline values at 24 hours (P<.02). Twenty-four hours after allergen challenge, all MRI-derived flow parameters were significantly lower in the control group compared to the asthma group (P<.05). HR, CO, and cardiac function parameters measured at 24 hours showed no significant difference comparing the two groups (P>.05). In asthmatic patients, MRI-derived hemodynamic parameters using phase-contrast MRI are slightly altered after segmental allergen provocation compared to normal controls indicating a mild systemic reaction to local allergen challenge.

Surfactant protein levels in bronchoalveolar lavage after segmental allergen challenge in patients with asthma

Allergic asthma is associated with airway inflammation and dysfunction of pulmonary surfactant. Because surfactant proteins (SP) account for immunomodulatory functions as well as biophysical functions, we hypothesized that the allergic response in asthma might be accompanied by a dysregulation of SPs. We measured levels of SP-A, SP-B, SP-C and SP-D by enzyme-linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid of 23 asthma patients and 10 healthy control subjects under well-controlled conditions before and 24 h after segmental allergen provocation. These data were related to surfactant function, Th(2) cytokine levels in BAL fluid and to the degree of eosinophilic inflammation. In patients with asthma, allergen challenge increased BAL levels of SP-B, SP-C and SP-D while SP-A was decreased. For SP-B and SP-D, a moderate increase was also observed after saline challenge. In contrast, no alterations were observed in healthy control subjects. Levels of SP-B and SP-C in asthmatics correlated with the ratio of small to large surfactant aggregates (SA/LA ratio) and correlated negatively with BAL surface activity. Furthermore, increased SP-C but not SP-B levels after allergen challenge correlated with eosinophil numbers, interleukin (IL)-5, and IL-13 in BAL while increased SP-D levels only correlated with eosinophil numbers. This study demonstrates significant alterations of all SPs in BAL fluid after allergen challenge of which SP-C was most closely related to surfactant dysfunction and the degree of the allergic inflammation.

Change In Plasma C5a Levels After Routine Allergen Immunotherapy Correlates With Dust Mite Dosage, Changes in Wheal Size, And Rhinoconjunctivitis Symptoms

RATIONALE: Complement split product C5a is increased in BAL fluid after segmental allergen provocation. C5a also is generated in vitro in serum in the presence of allergens. This study investigated if plasma C5a levels are altered after routine allergen immunotherapy (IT) for rhinitis/asthma.METHODS: C5a-desArg levels in plasma (ELISA) from IT subjects (n=16) were determined immediately before and 1 hr after IT. Skin reactivity to each allergen (induration) was determined at 15 min and 1 hr. Spirometry was performed before and at 1 hr. Rhinoconjunctivitis quality of life symptom scores (RQLQ, Juniper) and total serum IgE level were determined.RESULTS: Change in plasma C5a levels was found to correlate with change in total mean wheal diameter (p=0.05), total dust mite IT dose(p=0.04), and total RQLQ score (p=0.03). Change in C5a did not correlate with total IT dose or IgE.Although change in C5a levels did not correlate with spirometric parameters at 1 hr, there was a significant negative correlation between total mean wheal diameter change and change in peak flow (PEFR)(p=0.005). The mean change in wheal diameter induced by dust mite IT was negatively correlated with change in FEF25-75 (p=0.007), but not PEFR (p=0.4).CONCLUSIONS: The correlation of change in C5a levels with dust mite dosage, changes in wheal size, and symptoms scores strongly suggests that C5a is crucial in the maintenance of allergic inflammation. RATIONALE: Complement split product C5a is increased in BAL fluid after segmental allergen provocation. C5a also is generated in vitro in serum in the presence of allergens. This study investigated if plasma C5a levels are altered after routine allergen immunotherapy (IT) for rhinitis/asthma. METHODS: C5a-desArg levels in plasma (ELISA) from IT subjects (n=16) were determined immediately before and 1 hr after IT. Skin reactivity to each allergen (induration) was determined at 15 min and 1 hr. Spirometry was performed before and at 1 hr. Rhinoconjunctivitis quality of life symptom scores (RQLQ, Juniper) and total serum IgE level were determined. RESULTS: Change in plasma C5a levels was found to correlate with change in total mean wheal diameter (p=0.05), total dust mite IT dose(p=0.04), and total RQLQ score (p=0.03). Change in C5a did not correlate with total IT dose or IgE. Although change in C5a levels did not correlate with spirometric parameters at 1 hr, there was a significant negative correlation between total mean wheal diameter change and change in peak flow (PEFR)(p=0.005). The mean change in wheal diameter induced by dust mite IT was negatively correlated with change in FEF25-75 (p=0.007), but not PEFR (p=0.4). CONCLUSIONS: The correlation of change in C5a levels with dust mite dosage, changes in wheal size, and symptoms scores strongly suggests that C5a is crucial in the maintenance of allergic inflammation.

Local nitric oxide levels reflect the degree of allergic airway inflammation after segmental allergen challenge in asthmatics

Nitric oxide (NO) levels are increased in the exhaled air of asthmatics. As NO levels correlate with allergic airway inflammation, NO measurement has been suggested for disease monitoring. In patients with asthma, we previously demonstrated that intrabronchial treatment with a natural porcine surfactant enhanced airway inflammation after segmental allergen provocation. We studied whether local levels of NO reflect the degree of allergic airway inflammation following segmental allergen challenge with or without surfactant pretreatment. Segmental NO, as well as nitrite and nitrate in bronchoalveolar lavage (BAL) fluid, was measured before and after segmental challenge with either saline, saline plus allergen, or surfactant plus allergen in 16 patients with asthma and five healthy subjects. The data were compared with inflammatory BAL cells. Segmental NO levels were increased after instillation of saline (p < 0.05), or surfactant plus allergen in asthmatics (p < 0.05), and values were higher after surfactant plus allergen compared to saline challenge. Nitrate BAL levels were not altered after saline challenge but increased after allergen challenge (p < 0.05) and further raised by surfactant (p < 0.05), whereas nitrite levels were not altered by any treatment. Segmental NO and nitrate levels correlated with the degree of eosinophilic airway inflammation, and nitrate levels also correlated with neutrophil and lymphocyte numbers in BAL. In healthy subjects, NO, nitrite, and nitrate were unaffected. Thus, segmental NO and nitrate levels reflect the degree of allergic airway inflammation in patients with asthma. Measurement of both markers can be useful in studies using segmental allergen provocation, to assess local effects of potential immunomodulators.

Increase in killer‐specific secretory protein of 37 kDa in bronchoalveolar lavage fluid of allergen‐challenged patients with atopic asthma

Atopic asthma is linked to a T-helper type 2 dominated pathogenesis, but there is increasing evidence of Th1/Tc1-mediated processes in the aetiopathology of asthma. Killer-specific secretory protein of 37 kDa (Ksp37) is expressed in cytotoxic lymphocytes, selectively in the effector subsets of CD8+- and CD4+ T lymphocytes and in CD16+/CD56dim natural killer cells and gamma/delta T cells. This effector cell-specific expression of Ksp37 and its coexpression with perforin suggest that Ksp37 might be involved in processes mediated by cytotoxic cells. We hypothesize that Ksp37 could indicate the involvement of cytotoxic lymphocytes in the pathogenesis of atopic asthma, and investigated Ksp37 concentration in bronchoalveolar lavage fluid (BALF) collected 10 min, 18, 42 or 162 h after segmental allergen provocation and in serum of patients with atopic asthma (n=25). Ksp37 concentrations in BALF and serum were detected by ELISA. Flow cytometric analysis was used to assess numbers and cell subsets in BALF. Ksp37 increased significantly in BALF 10 min, 18 and 42 h, but not 162 h after allergen challenge compared with saline-challenged controls, while Ksp37 serum levels did not change significantly at all time-points. In addition, the increase in Ksp37 concentrations in BALF correlated with the corresponding numbers of lymphocytes. We conclude that Ksp37 level increased in BALF 10 min, 18 and 42 h after allergen challenge but not in peripheral blood. Our findings suggest that segmental allergen challenge in asthma is associated with an increase in Ksp37 concentrations in BALF and an influx of potentially cytotoxic T lymphocytes into the lungs.

Chemokine‐receptor expression on T cells in lung compartments of challenged asthmatic patients

The interaction of chemokines with their receptors strongly influences the migration of leucocytes. In order to assess the contribution of these molecules to the local recruitment of T cells in bronchial asthma, we analysed the expression of 14 chemokine receptors on lung-derived T cells. Chemokine-receptor expression by T cells derived from the peripheral blood, the bronchoalveolar lavage fluid and the bronchial mucosa was analysed by flow cytometry and immunohistochemistry. Expression profiles in healthy and mildly asthmatic individuals were compared, the latter prior and after segmental allergen provocation. Compared with peripheral blood, alveolar T cells expressed significantly more CCR2, CCR5, CCR6, CXCR3 and CCR4. However, no differences were observed between healthy controls and unchallenged asthmatics. In patients developing significant inflammatory responses following specific allergen challenge, a marked increase in the percentage of CCR4+ and CCR7+, and reduced numbers of CXCR3-bearing alveolar T cells were detected. Following specific allergen challenge, chemokine-receptor expression profiles of T cells from the alveolar space and the mucosa or the submucosa were similar, excluding a particular subcompartmentalization of the chemokine/chemokine-receptor system. The expression of certain chemokine receptors by lung T cells suggests a contribution to the physiological recruitment of T cells to the lungs, both in healthy controls and unchallenged mild asthmatics. However, strong allergen-induced airway responses were associated with a specific chemokine-receptor profile, suggesting the involvement of certain chemokine receptors in the pathogenesis of allergic bronchial inflammation.

Neurotrophins in allergic disease of skin and lung: modulators of immunological and neuronal plasticity

Allergies are chronic inflammatory disease of the skin, lung and gut. Atopic dermatitis represents the main manifestation of the skin, and bronchial asthma is the leading condition in the lower respiratory tract. Both conditions are due to an inappropriate immune response to harmless environmental antigens (or allergens). There is growing evidence for a close interaction between the immune and nervous system in the pathophysiology of allergies. Recent evidence from our group indicates that neurotrophin production including nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) are elevated in those organs. Both, residential cells including airway epithelium and migratory cells including macrophages, T cells and eosinophils serve as important sources. The effects of increased neurotrophin production are bidirectional. On the one hand, they control sensory nerve fibres in terms of function, neuropeptide synthesis and survival. On the other side, neurotrophins also serve as important survival factors particularly for inflammatory cells such as eosinophils, T cells and macrophages. Utilizing the model of segmental allergen provocation of mild to moderate asthmatic patients, it has been shown that neurotrophins prevent sufficiently apoptotic cell death of lung, but not blood eosinophils. In addition, they augment the ongoing inflammatory reaction. The functional interaction between neurotrophins and immune and nerve cells has been extensively studied in both human and mouse models of experimental allergic asthma. In the latter system, the crucial role of the pan‐neurotrophin receptor p75 has been investigated in p75 NTR–/– mice. Furthermore, NGF transgenic animals have been utilized to assess the contribution of NGF. The role of BDNF on differentiation and function of B‐lymphocytes has been identified in BDNF–/– mice. In conclusion, our data support the concept that neurotrophins mediate immunological and neuronal plasticity within the neuro‐immune network of allergic disease in the lung and skin.

Interleukin-5 receptors on human lung eosinophils after segmental allergen challenge.

IL-5 is a specific cytokine for eosinophil accumulation, activation and prolongation of survival and can be recovered in elevated concentrations from the bronchoalveolar compartment in atopic asthma following allergen challenge. The action of IL-5 is mediated via the specific IL-5 receptor-alpha (IL-5Ralpha). Although in vitro data suggest that IL-5R expression is regulated by cytokines such as IL-3, IL-5 and GM-CSF, IL-5R regulation in vivo and its kinetics following allergen provocation are incompletely understood. We investigated IL-5R regulation in vivo following segmental allergen provocation (SAP) with an individually standardized dose of allergen in 12 patients with atopic asthma. Lavage was performed 10 min and 18 h (eight patients) and 10 min and 42 h (eight patients) after allergen challenge. In addition to differential cell counts, IL-5Ralpha was measured by flow cytometry and IL-5 concentrations in bronchoalveolar lavage (BAL) fluid were determined by ELISA. IL-5Ralpha expression decreased significantly on peripheral blood and on BAL eosinophils 18 and 42 h after SAP. In contrast, IL-5 concentrations increased significantly in BAL fluid 18 and 42 h after SAP. In four and two patients, respectively, there were detectable IL-5 concentrations in serum 18 or 42 h after allergen exposure. Although there was no correlation between IL-5 concentrations and IL-5Ralpha expression on eosinophils in BAL, our data support previous in vitro and in vivo findings of a negative feedback mechanism between IL-5 concentrations and IL-5Ralpha expression on eosinophils.

Increase in granzyme B+ lymphocytes and soluble granzyme B in bronchoalveolar lavage of allergen challenged patients with atopic asthma.

Asthma has been linked to a chronic, T-cell-mediated bronchial inflammation. Because other T-lymphocyte-mediated, chronic inflammatory disorders have been associated with elevated granzyme B (grB) expression we tested the hypothesis that atopic asthma might be associated with elevated grB levels in the bronchoalveolar compartment. Therefore we performed intracellular grB staining in lymphocytes from bronchoalveolar lavage (BAL) collected 42 h after segmental allergen provocation (SAP) in allergic patients with bronchial asthma. There was a significant increase in CD3(+), CD8(+), and CD16/56(+) lymphocytes expressing grB in BAL 42 h after SAP as compared to saline challenged controls. However, compared to peripheral blood the percentages of these lymphocyte subsets detected as grB(+) in BAL remained significantly lower. Measurement of extracellular grB in BAL fluids by a particle immunoassay revealed significantly elevated grB levels in the allergen challenged bronchoalveolar compartment 42 h following SAP in six of the eight patients (range, <1.0-348.1 pg/ml) as compared to saline challenged controls (range, <1.0-70.5 pg/ml). We conclude that total cell numbers of grB(+) lymphocyte subsets increase 42 h after SAP in the lower respiratory tract. In addition there is evidence to suggest that grB is released into the airways of asthmatic patients. This suggests a role for grB in the pathophysiological processes following SAP but its definitive role in allergic bronchial asthma needs to be established.

Eosinophil cationic protein alters pulmonary surfactant structure and function in asthma

Background Impaired surfactant function has been demonstrated in patients with asthma. Inhibitory proteins originating from plasma or inflammatory mediators are good candidates to contribute to this dysfunction. Eosinophils are potent effector cells in asthma, which, on activation, release inflammatory mediators, especially reactive granula proteins such as eosinophil cationic protein (ECP). Objective Because the potential role of ECP in the inhibition of surfactant function is not known, we tested the hypothesis of whether ECP levels in bronchoalveolar lavage fluid (BALF) of patients with asthma after segmental allergen provocation correlate to surfactant dysfunction. Furthermore, we tested the effect of purified ECP on surfactant function and structure in vitro. Methods Surfactant isolated from BALF of asthmatic patients was assessed for biophysical function with the Pulsating Bubble Surfactometer and the Capillary Surfactometer and correlated to ECP levels. Purified ECP and plasma proteins at various concentrations were incubated with natural surfactant. Surfactant function was studied with the Capillary Surfactometer, and surfactant structure was determined by electron microscopy. Results ECP is elevated in BALF from patients with asthma after allergen challenge compared with baseline. ECP levels after allergen challenge correlate well to surfactant dysfunction. In vitro, ECP induces a concentration-dependent inhibition of surfactant function that can be inhibited by antibodies against ECP. ECP is more potent compared with albumin or fibrinogen. Finally, ECP induces severe ultrastructural changes to surfactant vesicles that are more pronounced than changes induced by either fibrinogen or albumin. Conclusions ECP contributes to surfactant dysfunction in asthma, which in turn could lead to airway obstruction.

The neurotrophins nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma.

Neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and NT-4) have been observed in elevated concentrations in allergic diseases. Neurotrophin levels are up-regulated endobronchially after allergen challenge. This coincides with an influx of activated eosinophils into the bronchial lumen. These eosinophils have an increased viability and CD69 expression 18 h after segmental allergen provocation (SAP) which is not present in peripheral blood. To investigate whether these observations are related we studied the influence of neurotrophins on eosinophil function in allergic asthma.Incubation with NGF, BDNF, NT-3, or NT-4 caused a significant increase in the viability and CD69 expression of isolated eosinophils from bronchoalveolar lavage fluid (BALF) but not from peripheral blood, suggesting a unique sensitivity of endobronchial eosinophils to neurotrophins. To elucidate the underlying mechanisms expression of the neurotrophin receptors p75NTR, trkA, trkB, and trkC on eosinophils was analyzed by RT-PCR and immunocytology. After SAP expression of all neurotrophin receptors was markedly elevated on eosinophils from BALF. Our findings suggest that neurotrophin-mediated activation of bronchial eosinophils might play a role in the regulation of eosinophilic inflammation in allergic asthma.

Local release of eosinophil peroxidase following segmental allergen provocation in asthma.

Eosinophil peroxidase (EPO) is an eosinophilic basic protein, which leads to increased permeability and damage of bronchial epithelial cells in asthma. As little is known about its local expression and release in humans the intracellular expression in lung and peripheral eosinophils and the concentrations of EPO in bronchoalveolar lavage (BAL) fluid and serum was investigated in patients with asthma. Twelve mild atopic asthmatic and nine control subjects underwent segmental sham and allergen challenge. EPO concentrations in BAL fluid and serum were determined by immunoassay and flow cytometry was used to determine the intracellular expression of EPO in BAL-derived and peripheral eosinophils. In asthmatic patients a large increase in BAL eosinophils--total cells: median 9.5 x 10(6) (range: 0.5 to 455.0 x 10(6)); relative: 38% (1 to 91%)--was detectable 24 h following allergen challenge, but peripheral blood eosinophil counts did not change. Concentrations of EPO in BAL fluid increased from 1 microg/L (1.0 to 6.8 microg/L) to 42 microg/L (5.6 to 379.6 microg/L; P < 0.01) after allergen but not after saline challenge (1.5 microg/L; 1.0 to 21.9 microg/L), whereas in control subjects all measurements were below the detection limit. Serum concentrations of EPO increased slightly from 18.3 microg/L (3.0 to 56.8 microg/L) to 27 microg/L (3.8 to 133.9 microg/L; P < 0.05) 24 h after allergen challenge in asthmatic patients. Furthermore, the intracellular expression of EPO (measured as mean fluorescence intensity) was decreased in BAL eosinophils compared with blood eosinophils (mean fluorescence intensity 29 (7 to 71) vs. 48 (20 to 85); P < 0.01) after allergen challenge. The finding of increased EPO concentrations in the BAL fluid and decreased intracellular EPO expression in pulmonary eosinophils of asthmatic patients reflects the allergen-triggered release of EPO into the bronchial space.

Neurotrophin-3 expression in human bronchoalveolar lavage fluid cells after segmental allergen provocation: Functional relevance for the inflammatory response in allergic asthma

Neurotrophin-3 expression in human bronchoalveolar lavage fluid cells after segmental allergen provocation: Functional relevance for the inflammatory response in allergic asthma

DIFFERENTIAL REGULATION OF AMINOPEPTIDASE N (CD13) BY TRANSENDOTHELIAL MIGRATION AND CYTOKINES ON HUMAN EOSINOPHILS

Aminopeptidase N (CD13) is a cell surface metalloprotease involved in growth regulation, tumor invasion, and down-regulation of regulatory peptides. CD13 expression on eosinophils in bronchoalveolar lavage (BAL) of asthmatics 10 minutes and 18 hours after segmental allergen provocation was significantly increased (+225% to +294%) compared to blood eosinophils. In vitro CD13 expression could be induced on blood eosinophils by transendothelial migration of the cells across interlenkin (IL) 1β-activated human umbilical cord vein endothelial cells (HUVECs) as well as by the exposure to the cytokines IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). The cytokines GM-CSF and IL-5 were significantly less effective in inducing CD13 compared to IL-3. The IL-3-induced expression of CD13 was decreased in the presence of the protein-synthesis inhibitor cycloheximide (−8.8%). Moreover, blocking of CD13 by the protease inhibitors actinonin and bestatin significantly enhanced migration (+40.0% to +80.0%) of eosinophils across HUVEC monolayers. In summary, the data suggest that CD13 is regulated both by the process of transmigration and by the cytokine IL-3. Further, CD13 itself seems to be involved in the process of eosinophil transmigration.

Complement factors C3a and C5a are increased in bronchoalveolar lavage fluid after segmental allergen provocation in subjects with asthma.

Allergic asthma is thought to be the result of an inappropriate specific immune response against common environmental antigens. However, studies of animal asthma models have also linked the innate immune system, in particular complement factors C3a and C5, to murine airway hyperresponsiveness. Because the possible role of these anaphylatoxins in patients with asthma is not understood, we tested the hypothesis that C3a and C5a will increase in the bronchoalveolar lavage (BAL) fluid of patients with asthma after segmental allergen provocation. In a group of 15 subjects with mild asthma we found a significant upregulation of C3a and C5a 24 h after allergen challenge compared with baseline values (p < 0.01). In a control group of healthy volunteers the concentrations remained basically unchanged. Furthermore, we found a strong correlation between both anaphylatoxins and the number of eosinophils (p < 0.01) and, to a lesser degree, with the number of neutrophils (p < 0.05) in BAL fluid. These data suggest a contribution of anaphylatoxins C3a and C5a to the pathogenesis in asthma. However, the pathogenic role of these substances in relation to asthma remains to be elucidated, for example, by using anaphylatoxin receptor blockers as a possible new therapeutic principle.

The interaction between upper and lower airways in allergic rhinitis

Introduction. The pathophysiological connections between allergic rhinitis and asthma are still not entirely understood. To elucidate these connections further, two provocation studies were performed in non-asthmatic allergic rhinitis patients. In the first study, we performed a segmental bronchial allergen provocation in seasonal allergic rhinitis subjects without asthma out of the grass pollen season. An increase in symptomatology was found not only in the lung but also in the nose. This increase in symptomatology was accompanied by a generalized inflammatory response, which was characterized by an increase in eosinophils and interleukin 5 (IL-5) expression, in the bronchial mucosa, the blood and nasal mucosa. In the second study, we investigated the effect of nasal allergen provocation on lower airways in allergic rhinitis patients. Again, an increase in blood and bronchial eosinophils, correlating with the local expression of adhesion molecules with the pulmonary symptom score, was found. Conclusion. Allergic rhinitis is not a local disease, but also influences the bronchial mucosa. It is probable that systemic induction of inflammatory mediators leads to a more generalized inflammatory response. This may explain why local treatment of the nose with anti-inflammatory drugs is also beneficial for the lower airways in allergic rhinitis patients with asthma.

CD69 surface expression on human lung eosinophils after segmental allergen provocation.

CD69 expression on eosinophils is observed in asthma and has been proposed as a marker of eosinophil activation. The role of allergens in the in vivo regulation of CD69 expression on eosinophils, however, remains incompletely understood. It was therefore investigated whether CD69 expression on eosinophils can be induced by allergen provocation in vivo. Ten allergic asthmatics were studied by segmental allergen provocation. Two segments of the right and left lung were challenged with allergen or saline. CD69 expression was determined by flow cytometry and concentrations of interleukins were analysed by enzyme-linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid. Expression of CD69 on BAL eosinophils in the segments lavaged 10 min following saline instillation (28.3+/-8.8 specific mean fluorescence (SMF)) was not significantly different to segments lavaged 10 min after allergen (80.2+/-21.8 SMF) and segments lavaged 18 h after saline challenge (87.2+/-23.3 SMF). However, CD69 expression on eosinophils increased significantly 18 h after allergen challenge (128.6+/-21.9 SMF, p<0.03) which was accompanied by elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations (114.9+/-42.9 pg x mL(-1), p<0.05). CD69 expression on eosinophils and GM-CSF concentrations correlated 18 h following allergen provocation (r = 0.7, p<0.025). These results suggest that in allergic asthma there is an allergen dependent, endobronchial upregulation of eosinophil activation as assessed by CD69 expression on eosinophils.

CD69 surface expression on human lung eosinophils after segmental allergen provocation

CD69 surface expression on human lung eosinophils after segmental allergen provocation