What is the role of the eosinophil?
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Asthma↗
Biomedical subjects
P Venge
Publications and source records attributed to P Venge.
Transfer of 99mTc DTPA and bronchoalveolar lavage findings in patients with asymptomatic extrinsic allergic alveolitis.
An investigation was performed to determine whether symptom free patients with previously diagnosed extrinsic allergic alveolitis had signs of inflammation in the lung. Pulmonary clearance of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (DTPA) was measured in seven patients with a history of extrinsic allergic alveolitis but with no symptoms at the time of the study and in 12 control subjects. Monoexponential clearance curves were obtained in all 12 control subjects. In contrast, lung clearance was abnormal in five of the seven patients: biexponential clearance curves were noted in four and an abnormally rapid monoexponential curve in one. Bronchoalveolar lavage was performed in all patients. Fluid from the second and third aliquots showed increased concentrations of albumin and urea in fluids from the patients, suggesting increased plasma leakage through the alveolocapillary membranes. More eosinophils and more eosinophil cationic protein were also found in the lavage fluid from the patients. The trend towards increased numbers of eosinophils in patients with abnormal lung clearance of DTPA suggests that this may be due to a continuing inflammatory reaction. Lung inflammation was also suggested by the fact that less leukotriene B4 was secreted by cultured alveolar macrophages obtained from patients than by control macrophages. It is concluded that symptom free patients with previous extrinsic allergic alveolitis have continuing alveolar disease as shown by lung clearance and lavage findings.
Adult↗
Inflammatory cells and eosinophilic activity in asthmatics investigated by bronchoalveolar lavage. The effects of antiasthmatic treatment with budesonide or terbutaline.
We investigated the constituents of bronchoalveolar lavage (BAL) regarding cell profiles and released eosinophilic cationic protein (ECP) in 11 patients treated occasionally with inhaled bronchodilators (Group A) and 11 patients treated regularly with inhaled corticosteroids (Group B). A normal, healthy control group of 12 subjects was also recruited. Compared with Group A, Group B had a reduced recovery percentage of infused volume (p less than 0.05) and total cell number (p less than 0.01). Compared with the control group, there was a significant increase in the percentage of eosinophils (p less than 0.05) in both groups of asthmatics. In Group A there was also a significant increase in mast cells (p less than 0.05), serum-ECP (p less than 0.05), and BAL-ECP (p less than 0.001). No correlations between any of the cell variables and the level of airway responsiveness measured as PC20 histamine were found in any group. Group A patients were investigated twice--before and after 4 wk of randomly allocated treatment with either a regular beta-2-receptor agonist (terbutaline 250 micrograms, two puffs four times a day) or a regularly inhaled corticosteroid (budesonide 200 micrograms twice a day). The BAL differential cell counts were similar and not significantly affected by either treatment. However, BAL-ECP levels were decreased by budesonide treatment (p less than 0.05). ECP levels in serum and BAL were significantly correlated (p less than 0.05 to 0.001). The eosinophilic cell involvement in asthma is further emphasized by this study but the increase in numbers of eosinophils seems less important than their activity, here measured as release of one degranulation product, ECP. To suppress disease activity, repeated long-term treatment is important, but clear preference for either treatment cannot be given on the basis of our present results.
Adult↗
Inflammatory system activation during cardiopulmonary bypass as an indicator of biocompatibility: a randomized comparison of bubble and membrane oxygenators.
As the exposure of blood to foreign material during cardiopulmonary bypass (CPB) leads to triggering of inflammatory systems, the inflammatory response was used as an indicator of the biocompatibility of oxygenators. Activation of complement and neutrophil granulocytes during CPB was studied in 96 patients undergoing coronary bypass, with randomized comparisons between four different oxygenators, two of bubble and two of membrane type. Seven patients undergoing thoracotomy without CPB served as controls. During CPB there was significant complement activation, measured as changes in the ratio C3d/C3, with no demonstrable difference between the bubble and membrane oxygenator groups. Such change was not seen in the controls. Neutrophil granulocytes released significant amounts of the granule proteins lactoferrin and myeloperoxidase during CPB, but not during thoracotomy without CPB. The plasma concentrations of lactoferrin and myeloperoxidase were significantly lower in the membrane oxygenator groups, possibly indicating better biocompatibility. The strong inflammatory response with both oxygenator types, however, indicates that presently used CPB devices have unsatisfactory biocompatibility.
Adult↗
Bubble and membrane oxygenators--comparison of postoperative organ dysfunction with special reference to inflammatory activity.
Bubble and membrane oxygenators (2 types of each) were compared in a randomized study of 96 patients undergoing coronary bypass grafting. Cardiac performance, assessed from postoperative need of inotropic support, was significantly better in the membrane oxygenator group. After perfusion lasting more than 2 hours, respiratory function, measured as alveolar-arterial oxygen pressure gradient, was less compromised in that group and renal function, quantified as postoperative rise of serum creatinine was less disturbed. Cerebral function, studied in terms of psychometric test results and concentration of adenylate kinase in cerebrospinal fluid, did not differ between the bubble and membrane oxygenator groups. In investigations concerning changes in inflammatory activity during bypass, complement activation could not be related to the mentioned clinical parameters. Release of the neutrophil granulocyte factors lactoferrin and myeloperoxidase was greater in the bubble oxygenator group and correlated to impaired cardiac and renal performance, but not to pulmonary or cerebral dysfunction.
Adult↗
Effects of UVB treatment on neutrophil function in psoriatic patients and healthy subjects.
To evaluate if whole body UVB irradiation has effects on the neutrophil function, eleven patients with mild to moderate psoriasis and 14 healthy subjects were treated with whole body UVB irradiation 3 times weekly for 4 weeks. Eight healthy untreated subjects served as controls. After 2 weeks of treatment the individual change of phagocytosis measured by the ingestion of IgG-coated particles was related to the pre-treatment value both in the psoriatic patients and healthy subjects (p less than 0.05 and p less than 0.001, respectively). Similar results were obtained for ingestion of IgG-C3b-coated particles. Thus, the change in phagocytic rate seemed to be dependent on the functional activity before treatment. UV irradiation of PMNs in vitro did not influence the phagocytic rate. After 4 weeks of UV treatment the healthy subjects showed a significant decrease in the rate of phagocytosis of IgG-C3b particles (p less than 0.02) and of the serum chemokinetic activity (p less than 0.01). In the psoriatic patients the mean chemokinetic activity in heated sera was decreased after 2 weeks (p less than 0.02). There appeared to be no relation between improvement of psoriasis and changes in PMN function. In an untreated group of healthy subjects no significant changes in neutrophil function were found. The results indicate that there is a change in PMN function during UVB treatment. The degree of change seems to vary, not only between individuals but possibly also between groups, e.g. healthy subjects compared with psoriatic patients.
Adult↗
[Degranulation of human eosinophilic granulocytes by the platelet activating factor].
Incubation of purified human eosinophil granulocytes (greater than 93%) with the platelet activating factor (PAF), led at concentrations of 1 pM to 10 microM, to a non-cytotoxic and dose-dependent liberation of proteins both from the "small" and the "specific" granules. The mean EC50 for this PAF-induced effect was 1.47 nM (n = 9), with a maximum at 100 nM PAF. The degranulating effect of PAF can be inhibited competitively by the specific PAF-receptor antagonist, WEB 2086 (KB between 12 and 13 nM), and is Ca2(+)-dependent.
Cell Degranulation↗
Human eosinophil-derived neurotoxin and eosinophil protein X are likely the same protein.
The human eosinophil granule contains a series of cationic proteins. Two of these, eosinophil-derived neurotoxin (EDN) and eosinophil protein X (EPX), are reported to have similar m.w. and both possess neurotoxic and helminthotoxic activities. Therefore, the properties of these molecules were analyzed to determine whether they differ. EDN was purified from eosinophils of patients with the hypereosinophilic syndrome and EPX from the buffy coat cells of normal individuals. By SDS-PAGE, both proteins showed a major band at 18.7 kDa and a minor band at 21.4 kDa. By two-dimensional non-equilibrium gel electrophoresis the proteins migrated identically. With radiolabeled proteins in reverse phase HPLC, both proteins eluted at the same concentration of acetonitrile and showed identical tryptic maps. Both proteins possessed comparable ribonuclease activity and both were comparably neurotoxic in the rabbit. By immunodiffusion the two proteins showed a reaction of identity; by RIA, with both polyclonal and monoclonal antibodies, the proteins had very similar inhibitory activities. These results indicate that EDN and EPX have virtually identical properties and are probably the same protein.
Animals↗
Stimulation of degranulation from human eosinophils by platelet-activating factor.
Platelet-activating factor (PAF) is a highly active mediator which has been implicated in allergic inflammation and bronchial asthma, possibly by interacting with eosinophils. We have examined the effect of PAF on activation of purified human eosinophils as measured by degranulation (eosinophil peroxidase, eosinophil cationic protein, arylsulfatase B, beta-glucuronidase, and alkaline phosphatase) and oxidative metabolism (superoxide anion production). PAF induced enzyme release at concentrations ranging from 1 pM to 10 microM in a rapid (t1/2 5 to 8 min), Ca2+-dependent and noncytotoxic manner from both the specific and small granules, whereas its biologic precursor and metabolite, lyso-PAF, had no effect. For all enzymes, maximal enzyme release occurred at 100 nM PAF with a mean ED50 value of 1.47 +/- 0.4 nM. At this concentration the mean percentage of total enzyme release by PAF from specific granules was 20.3 +/- 1.6% (17.9% for eosinophil peroxidase, 20.6% for beta-glucuronidase, 22.4% for alkaline phosphatase) and 28.8 +/- 2.2% from small granules (arylsulfatase B). Calcium ionophore A23187, PMA, and opsonized zymosan also induced eosinophil degranulation but their peak effect after 10-min incubation with maximal release 14.7%, 12.9%, or 14.1%, respectively, was lower when compared with PAF. Incubation of eosinophils with the PAF-antagonist WEB 2086 led to a parallel shift of the dose-response curve to the right, indicating a competitive antagonism. PAF also caused generation of superoxide anions by human eosinophils but this occurred at higher concentrations of PAF (1 microM to 30 microM) with an ED50 of 8.4 +/- 0.9 microM. Again, this effect was competitively inhibited by WEB 2086. These studies demonstrate that PAF activates human eosinophils to release granule constituents and generate superoxide anions. Since both PAF and eosinophil products are associated with pathogenesis of bronchial asthma our findings may be of particular pathophysiologic relevance.
Alkaline Phosphatase↗
Glutathione in bronchoalveolar lavage fluid from smokers is related to humoral markers of inflammatory cell activity.
Cigarette smoking results in variable degrees of inflammation in the lower respiratory tract. Furthermore, smoking produces oxidant-mediated changes in the lung, important to the pathogenesis of emphysema. Since glutathione can neutralize reactive oxygen species and prevent peroxidation of unsaturated lipids, it may constitute an important component of the lung's defense against oxidant and inflammatory injury. In the present study, broncholaveolar lavage (BAL) was performed in 27 smokers, and the concentrations of total glutathione as well as the cellular and humoral markers of inflammatory activity were studied. There were significant correlations between total glutathione and neutrophils; two neutrophil granule components, myeloperoxidase and elastase; and chemotactic activity for neutrophils. Moreover, the total glutathione correlated with the eosinophil cationic protein (ECP), a granule constituent of the eosinophil, with two locally produced antiproteases, secretory leukocyte protease inhibitor (SLPI) and antichymotrypsin (ACHY), but not with an alpha 1-protease inhibitor and albumin. These data suggest that the total glutathione levels in BAL fluid may reflect a degree of oxidative and inflammatory stress caused by cigarette smoke, and they are therefore likely to contribute to the protection against this stress.
Biomarkers↗
Metal content of neutrophil granules is altered in chronic inflammation.
The mass fraction of certain elements was measured in isolated granulocytes and isolated granulocyte granule fractions from patients with active inflammatory arthritides (N = 6) and healthy controls (N = 6). The patients had significantly increased amounts of Ca in the granulocytes, in the specific and light azurophil granules, but normal Ca amounts in the dense azurophil granules. Sr was below the detection limit in the granulocytes and granule fraction from controls, but it appeared in high concentrations in the granulocytes and all granule fractions from the patients. The patients had considerably increased granulocyte amounts of Mn but only slightly increased Mn concentrations in the specific granules. Mn was not detectable in azurophil granules from patients and controls. A prominent accumulation of Fe was seen in the granulocytes from the patients, together with an Fe accumulation in the specific granules. Fe was below the detection limit in azurophil granules from patients and controls. The patients had reduced granulocyte Zn and reduced amounts of Zn in the dense and light azurophil granules but normal Zn amounts in the specific granules. The results obtained indicate that the granulocyte accumulation of Ca, Sr, and Fe observed during chronic inflammation is associated with corresponding granule accumulation of these metals; the considerable Mn accumulation in granulocytes during inflammation is not localized in their granules; and the granule subpopulations differ in their capacity to store certain metals.
Arthritis↗
Serum levels of neutrophil and eosinophil chemotactic activities in mastocytosis.
Neutrophil and eosinophil chemotactic activities (NCA and ECA) were measured in serum from twenty-two patients with urticaria pigmentosa or systemic mastocytosis. NCA was also measured after heating serum to 56 degrees C (heat-stable NCA). Although these factors were increased in about half of the patients there was no correlation with histamine release as estimated by the excretion of the main histamine metabolite methylimidazoleacetic acid (MelmAA) in urine. A significant increase in heat-stable NCA, however, was found in patients with pruritus and abnormal high values of MelmAA. It is concluded that only heat-stable NCA is a specific mast cell mediator, but that the heat-labile NCA and ECA are dependent on mast cells for their production by a different cell, tentatively identified as the macrophage.
Adult↗
Neutrophil and eosinophil involvement of the small bowel in patients with celiac disease and Crohn's disease: studies on the secretion rate and immunohistochemical localization of granulocyte granule constituents.
PURPOSE: The concentrations of myeloperoxidase (MPO), a neutrophil granule constituent, and eosinophil cationic protein (ECP), a specific eosinophil granule protein, were measured in jejunal perfusion fluid in an attempt to elucidate the neutrophil and eosinophil involvement of the small bowel in health and disease. PATIENTS AND METHODS: The control group consisted of 14 males and two females. Ten patients (seven males and three females) with Crohn's disease and seven patients (two males and five females) with celiac disease were also studied; in addition, one patient with relapsing giardiasis, one patient with giardiasis and complete absence of plasma cells in small intestinal lamina propria, and one patient with selective IgA deficiency and no IgA plasma cells in duodeno-jejunal lamina propria were evaluated. Segmental perfusion of the jejunum was performed according to a previously described method. MPO and ECP were measured by radioimmunoassays. RESULTS: In healthy control subjects, the concentrations of both granule proteins were in a narrow range and much higher than would have been anticipated from passive leakage from circulating blood. In patients with celiac disease, the perfusion fluid concentrations of MPO and ECP were on average 3.5 and eight times, respectively, higher than the values seen in the controls. The jejunal segment perfused in patients with Crohn's disease was endoscopically and histologically normal. The perfusion fluid concentrations of MPO and ECP were increased 3.5 and two times, respectively, compared with that in the control subjects. Both patient groups and the control group had similar perfusion fluid concentrations of albumin. Data on MPO and ECP expressed as jejunal secretion rates gave the same differences between patients and controls as just described for the jejunal fluid concentrations. Immunohistochemical studies of jejunal biopsy specimens from another group of patients with celiac disease demonstrated a prominent extracellular deposit of ECP in the lamina propria of the atrophic intestinal mucosa, whereas the release of neutrophil constituents (cathepsin G, MPO) was scarce. In Crohn's disease, an extracellular degranulation of ECP and, to a lesser extent, of cathepsin G was observed in relation to ulcerations only. CONCLUSION: Data obtained indicate that the local release of neutrophil and eosinophil granule components is enhanced in the jejunal tissue from patients with celiac sprue and Crohn's disease. The prominent extracellular deposit of eosinophil granule constituents with cytotoxic properties at the site of inflammatory intestinal lesions in celiac sprue might reflect a pathophysiologic mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Angiostrongylus cantonensis: role of eosinophils in the neurotoxic syndrome (Gordon-like phenomenon).
The role of eosinophils in the pathophysiology of Angiostrongylus cantonensis infections was investigated in nonpermissive (guinea pig) and permissive (rat) hosts. Neurological symptoms similar to the Gordon phenomenon (ataxia, tremor, paralysis) together with a loss of Purkinje cells in the cerebellum were observed after intracraneal injection of human eosinophil extracts or after infection with A. cantonensis, only in guinea pigs and not in rats. Blood eosinophilia as well as eosinophil numbers present in the cerebellum and in the cerebrospinal fluid were higher in guinea pigs than in rats, at all times after infection with A. cantonensis. Increased levels of cytotoxicity toward L3 larvae in vitro were obtained in the presence of guinea pig eosinophils and IgE antibodies, rather than with the corresponding rat effector system. The detection of one eosinophil granule component, the eosinophil peroxidase, in the cerebrospinal fluid from infected guinea pigs but not from rats suggested that in nonpermissive hosts, neurological disorders, similar to the previously described Gordon phenomenon, might be due to eosinophil neurotoxins released after interaction of eosinophils with the parasites.
Angiostrongylus↗
The formation of eosinophil and neutrophil chemotactic activity during a pollen season and after allergen challenge.
Heat-stable (HS) and heat-labile (HL) neutrophil chemotactic activities (NCAs) have been demonstrated in serum after allergen challenge of subjects with asthma. In this investigation, we have studied the possible occurrence of similar activities in 20 atopic individuals on natural exposure to allergen, that is, during the birch-pollen season. Since eosinophil accumulation is a hallmark of an ongoing allergic inflammation in the respiratory tract also, the possible production of eosinophil chemotactic activity (ECA) was examined in serum after allergen challenge and at natural exposure to pollen. Both HL-NCA and HL-ECA were produced to a significant extent (p less than 0.001) during the season, with the peak of activities occurring simultaneously with the peak pollen count. HL-ECA was produced after allergen challenge of subjects with asthma in the laboratory, as has been demonstrated for NCA previously. The activity of the HS-NCA was unaltered during season. Gel-filtration studies of the major HL-NCA and HL-ECA indicated a molecular weight for both activities of 100 to 150,000, and the activities produced during season cochromatographed with the HL-NCA and HL-ECA produced after allergen challenge in the laboratory, suggesting that all these activities are due to one and the same molecule. The results suggest that the heat-labile chemotactic activity found in serum of atopic subjects and subjects with asthma after allergen exposure may be involved in the attraction of eosinophils and neutrophils to the site of allergic inflammation.
Asthma↗
Challenge with gliadin induces eosinophil and mast cell activation in the jejunum of patients with celiac disease.
PURPOSE: The aim of this study was to clarify the role of eosinophils and mast cells in the small bowel in celiac disease. PATIENTS AND METHODS: Patients with celiac disease (n = 10) were investigated by perfusion of a closed jejunal segment. The concentrations of certain granule constituents from eosinophils, eosinophil cationic protein (ECP), and from mast cells/basophils, histamine, were measured and the jejunal secretion rates of these cellular markers were calculated. RESULTS: Compared with findings in healthy control subjects (n = 14), increased secretion rates were observed under basal conditions in patients with histopathologically active celiac disease. Gliadin, administered by perfusion to the jejunal segment, induced a fourfold increase in ECP secretion and a twofold increase of histamine secretion in patients with celiac disease (n = 7), but did not influence the secretion rates of these substances in healthy controls (n = 3). The secretion rate of ECP started to increase 20 minutes after challenge of the perfused segment with gliadin and reached maximum levels 40 minutes later. The secretion rate of histamine started to increase 40 minutes after gliadin administration. Concurrently with these inflammatory events, the secretion of albumin was doubled as a sign of increased mucosal leakage. CONCLUSION: These data indicate that eosinophils and mast cells are both involved in the early gliadin-induced reactions of the small intestine, and suggest that these cells are effector cells participating in the celiac lesion of the mucosa.
Adult↗
Lucigenin-enhanced chemiluminescence in blood is increased in cancer.
The production of oxygen-derived cytotoxic metabolites by phagocytic cells is probably important in cancer cell killing. This production can be measured by chemiluminescence (CL). In the present report the authors have measured luminol and lucigenin-enhanced CL in whole blood from 63 untreated patients with cancer. In particular, the lucigenin-enhanced CL was increased in patients with cancer (P less than 0.001). No relation to origin or spread of the cancer was obvious. Monocyte number in peripheral blood was also significantly (P less than 0.01) increased as compared with age-matched controls. Further, the lucigenin-enhanced CL of purified monocytes, but not that of purified polymorphonuclear leukocyte(s) (PMNs), correlated significantly (P = 0.002) with the activity of whole blood. The authors conclude therefore that the highly increased lucigenin-enhanced CL observed in whole blood of a patient with cancer may reflect the enhanced production and activity of circulating monocytes that is a consequence of the body's defense reactions toward the developing cancer.
Acridines↗
Eosinophils and eosinophil cationic protein in nasal lavages in allergen-induced hyperresponsiveness: effects of topical glucocorticosteroid treatment.
Airway challenges with allergen are frequently followed by an increase in responsiveness to both specific and unspecific stimuli. This phenomenon in the lower airways has been linked to the presence of a late phase response to allergen challenge. One of the hallmarks of the late phase response is a tissue infiltration of granulocytes, specifically the eosinophils. A hypothesis for the increase in responsiveness has been that local activation of these eosinophils with subsequent release of the toxic granular constituents leads to a decrease in the barrier function of the airway epithelium. The aim of the present study was to further explore this hypothesis. Ten patients with previously demonstrated nasal allergen-induced hyperresponsiveness participated in a double-blind cross-over study involving pretreatment for various periods with topical glucocorticosteroids. The patients were challenged intranasally with allergen on one day, rechallenge 24 h later and the increase in responsiveness noted. In a nasal lavage performed immediately prior to challenge the number of eosinophilic granulocytes and the level of eosinophilic cationic protein (ECP) was determined. As expected, the placebo-treated patients demonstrated an increase in nasal responsiveness at rechallenge accompanied by a tendency for an increase in eosinophils as well as ECP in the lavage preceding the rechallenge compared with the initial allergen challenge 24 h previously. The amount of ECP found in the lavage on the second day correlated with the TAME-esterase activity, a marker of ongoing inflammatory activity (r = 0.64; P less than 0.05) in the same lavage, suggesting participation of the eosinophilic granulocyte in the inflammatory response to allergen.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Topical↗