Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EOSINOPHILS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMedDate not supplied

Eosinophils and eosinophil-associated cytokines in allergic inflammation.

Eosinophils are major effector cells in allergic tissue reactions. Their capacity to synthesize and store cytokines, particularly Th2-type cytokines, which may have autocrine effects such as increased cell survival in tissues, is of particular current interest. We have shown that eosinophils infiltrating the site of human cutaneous late-phase reactions (LPR) express mRNA and protein product for IL-4 and IL-5. Stimulation of peripheral blood eosinophils in vitro with either IgG or sIgA produces time-dependent induction of IL-4 and IL-5 transcription, indicating that mature cells may undergo local cytokine synthesis. We also demonstrated that bronchial biopsies from patients with both atopic and non-atopic (intrinsic) asthma express IL-4 and IL-5 mRNA which mainly co-localized to T cells, although clear hybridization signals were also obtained with eosinophils and mast cells. On the other hand, immunoreactivity for the corresponding protein was detectable predominantly in eosinophils and mast cells; a finding believed to reflect granule storage of cytokines. We also studied the resolution of the cutaneous LPR. Apoptosis of eosinophils persisted slightly longer than neutrophils in the tissues. The eventual decline in both neutrophil and eosinophil numbers followed on from the peak of the LPR. This was associated with terminal-deoxynucteotidyl-transferase-mediated nick and labelling positive (TUNEL+) (apoptotic) cells with the subsequent removal of apoptotic neutrophils and eosinophils by tissue macrophages. Thus, IL-4 and IL-5 production by eosinophils may amplify local allergic inflammatory responses and, in the case of IL-5, may prolong local tissue survival. However, in the allergen-induced LPR, inflammation rapidly resolves, possibly through the initiation of programmed cell death and phagocytosis of apoptotic cells by macrophages.

Asthma↗
PubMed1975

Behavior of eosinophil leukocytes in acute inflammation. II. Eosinophil dynamics during acute inflammation.

The marked diminution in the number of circulating eosinophils, which has been shown to occur during acute bacterial infections, is a distinctive aspect of eosinophil physiology and of the host response to acute infection. The mouse rendered eosinophilic by infection with trichinosis provides a suitable model for study of the eosinopenic response induced by acute inflammation. The alterations in eosinophil dynamics associated with acute inflammatory reactions in trichinous mice were studied with pneumococcal abscesses, with Escherichia coli pyelonephritis, with Coxsackie viral pancreatitis, and with acute subcutaneous inflammation due to turpentine. Each of these stimuli of acute inflammation markedly suppressed the eosinophilia of trichinosis. This suggests that the eosinopenia is a response to the acute inflammatory process rather than the response to a specific type of pathogen. These studies apply quantitative techniques to ascertain the effects of acute inflammation on eosinophil production in bone marrow and on distribution of eosinophils in the peripheral tissues. From these observations, it is apparent that the initial response to acute inflammation includes a rapid drop in numbers of circulating eosinophils, a rapid accumulation of eosinophils at the periphery of the inflammatory site, and an inhibition of egress of eosinophils from the bone marrow. With prolongation of the inflammatory process, inhibition of eosinopoiesis occurs.

Acute Disease↗
PubMed2002

Stem cell factor can stimulate the formation of eosinophils by two types of murine eosinophil progenitor cells.

There are only three known stimuli for eosinophil formation-GM-CSF, interleukin-5 (IL-5), and IL-3. Because mice with inactivation of the gene encoding the common beta receptor chain for GM-CSF, IL-5, and IL-3 (betac(-/-) mice) cannot respond to GM-CSF or IL-5 and do not produce IL-3, they should lack eosinophils. However, they produce reduced numbers of eosinophils, indicating the existence of at least one additional stimulatory factor. Use of betac(-/-) mouse marrow cells failed to detect a novel eosinophil-stimulating factor in cell line- or organ-conditioned media, but stem cell factor (SCF) was found to have a previously unrecognized ability to stimulate the formation of eosinophil colonies or mixed neutrophil-eosinophil colonies. This action of SCF was also observable with marrow cells from other mouse strains and was enhanced by the addition of G-CSF but no other factor tested. Recloning of SCF-stimulated blast colonies showed that progenitors forming pure eosinophil or mixed neutrophil-eosinophil colonies can have a common ancestor but many appear to arise independently from different preprogenitor cells. The observed activity of SCF in marrow cultures was relatively weak, but its action may be stronger in vivo, and SCF needs to be added to GM-CSF, IL-5, and IL-3 in the list of cytokines able to stimulate eosinophil formation.

Animals↗
PubMed1997

Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces eosinophil chemotaxis.

The effects of recombinant human (rh) interleukin (IL)-4 or rhIL-13 on survival, and chemotactic activity of human eosinophils were examined. Only rhIL-13 prolonged eosinophil survival in a dose-dependent manner above 3 ng/ml. Eosinophil survival induced by rhIL-13 was inhibited by monoclonal antibodies (mAbs) against IL-3 (p < 0.01) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.05), suggesting that rhIL-13 induced IL-3 and GM-CSF production from eosinophils and an autocrine mechanism is responsible for the eosinophil survival. The effects of rhIL-13 on eosinophil chemotactic activity were also examined. rhIL-13 showed chemotactic activity for eosinophils in a dose-dependent manner. Checkerboard analysis revealed that eosinophil migration was dependent on the concentration gradient, confirming that rhIL-13 is a chemotactic factor. rhIL-4 showed no effects. IL-13 may play an important role in the survival and recruitment of eosinophils in allergic diseases.

Cell Degranulation↗
PubMed2001

Human eosinophils and human high affinity IgE receptor transgenic mouse eosinophils express low levels of high affinity IgE receptor, but release IL-10 upon receptor activation.

FcepsilonRI expressed by human eosinophils is involved in IgE-mediated cytotoxicity reactions toward the parasite Schistosoma mansoni in vitro. However, because receptor expression is low on these cells, its functional role is still controversial. In this study, we have measured surface and intracellular expression of FcepsilonRI by blood eosinophils from hypereosinophilic patients and normal donors. The number of unoccupied receptors corresponded to approximately 4,500 Ab binding sites per cell, whereas 50,000 Ab binding sites per cell were detected intracellularly. Eosinophils from patients displayed significantly more unoccupied receptors than cells from normal donors. This number correlated to both serum IgE concentrations and to membrane-bound IgE. The lack of FcepsilonRI expression by mouse eosinophils has hampered further studies. To overcome this fact and experimentally confirm our findings on human eosinophils, we engineered IL-5 x hFcepsilonRIalpha double-transgenic mice, whose bone marrow, blood, spleen, and peritoneal eosinophils expressed FcepsilonRI levels similar to levels of human eosinophils, after 4 days culture with IgE in the presence of IL-5. Both human and mouse eosinophils were able to secrete IL-10 upon FcepsilonRI engagement. Thus, comparative analysis of cells from patients and from a relevant animal model allowed us to clearly demonstrate that FcepsilonRI-mediated eosinophil activation leads to IL-10 secretion. Through FcepsilonRI expression, these cells are able to contribute to both the regulation of the immune response and to its effector mechanisms.

Animals↗
PubMed2003

Delta 12-prostaglandin J2, a plasma metabolite of prostaglandin D2, causes eosinophil mobilization from the bone marrow and primes eosinophils for chemotaxis.

PGD(2), a major mast cell mediator, is a potent eosinophil chemoattractant and is thought to be involved in eosinophil recruitment to sites of allergic inflammation. In plasma, PGD(2) is rapidly transformed into its major metabolite delta(12)-PGJ(2), the effect of which on eosinophil migration has not yet been characterized. In this study we found that delta(12)-PGJ(2) was a highly effective chemoattractant and inducer of respiratory burst in human eosinophils, with the same efficacy as PGD(2), PGJ(2), or 15-deoxy-delta(12,14)-PGJ(2). Moreover, pretreatment of eosinophils with delta(12)-PGJ(2) markedly enhanced the chemotactic response to eotaxin, and in this respect delta(12)-PGJ(2) was more effective than PGD(2). delta(12)-PGJ(2)-induced facilitation of eosinophil migration toward eotaxin was not altered by specific inhibitors of intracellular signaling pathways relevant to the chemotactic response, phosphatidylinositol 3-kinase (LY-294002), mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (U-0126), or p38 mitogen-activated protein kinase (SB-202190). Desensitization studies using calcium flux suggested that delta(12)-PGJ(2) signaled through the same receptor, CRTH2, as PGD(2). Finally, delta(12)-PGJ(2) was able to mobilize mature eosinophils from the bone marrow of the guinea pig isolated perfused hind limb. Given that delta(12)-PGJ(2) is present in the systemic circulation at relevant levels, a role for this PGD(2) metabolite in eosinophil release from the bone marrow and in driving eosinophil recruitment to sites of inflammation appears conceivable.

Aniline Compounds↗
PubMed1999

[A mechanism for the anti-inflammatory effect of nedocromil; inhibition of both adhesion molecule expression on eosinophils and endothelial cells, and eosinophil chemotactic activities].

The accumulation of eosinophils in the airway is one of the characteristics seen in patients with bronchial asthma. One of the newly developed anti-asthma drugs (controller), nedocromil sodium (nedocromil) is known to suppress the influx of eosinophils into allergic lesions. However, little is known about this mechanism. Therefore, in this report we investigated the effects of nedocromil on Mac-1 expression on PAF-stimulated eosinophils, and adhesion molecule expression on endothelial cells stimulated by either IL-1 beta or IL-4. We also investigated the eosinophil chemotaxis. A significant suppression of the Mac-1 expression on PAF-induced eosinophils was observed at both concentrations of 10(-5) and 10(-7) M of nedocromil. The expression of adhesion molecules, particularly ICAM-1 and E-selectin, on IL-1 beta-stimulated human umbilical vascular endothelial cells (HUVEC) was significantly suppressed at these concentrations, whereas the VCAM-1 expression was not changed. No significant suppression of VCAM-1 expression on IL-4-stimulated HUVEC was observed, although there was a tendency of suppression at these concentrations. On the other hand, the expression of the E-selectin molecule was significantly suppressed by nedocromil even under resting (non-stimulated) condition. PAF-induced eosinophil chemotactic activities were also suppressed at these concentrations in a dose-dependent manner. These results suggested that nedocromil suppressed the influx of eosinophils to inflammatory lesions by inhibiting not only the expression of the Mac-1 on eosinophils and of E-selectin and ICAM-1 molecules on HUVEC, but also the eosinophil chemotactic activities.

Anti-Asthmatic Agents↗
PubMed2000

VCAM-1 has a tissue-specific role in mediating interleukin-4-induced eosinophil accumulation in rat models: evidence for a dissociation between endothelial-cell VCAM-1 expression and a functional role in eosinophil migration.

Eosinophil accumulation has been associated with the pathogenesis of numerous allergic inflammatory disorders. Despite the great interest in this response, many aspects of eosinophil accumulation remain unknown. This is particularly true with respect to tissue-specific mechanisms that may regulate the accumulation of eosinophils in different organs. This study addressed this issue by investigating and comparing the roles of alpha(4)-integrins and vascular cell adhesion molecule 1 (VCAM-1) adhesion pathways in interleukin 4 (IL-4)-induced eosinophil accumulation in 2 different rat models of inflammation, namely pleural and cutaneous inflammation. Similar to our previous findings in studies in rat skin, locally administered IL-4 induced a time- and dose-dependent accumulation of eosinophils in rat pleural cavities, a response that was associated with generation of the chemokine eotaxin. The IL-4-induced eosinophil accumulation in skin and pleural cavities was totally inhibited by an antirat alpha(4)-integrins monoclonal antibody (mAb) (TA-2). In contrast, whereas an antirat VCAM-1 mAb (5F10) totally blocked the response in skin, IL-4-induced eosinophil accumulation in rat pleural cavities was not affected by VCAM-1 blockade. A radiolabeled mAb technique demonstrated that endothelial-cell VCAM-1 expression was induced in response to IL-4 in both skin and pleural membrane. The results indicate that although endothelial-cell VCAM-1 is present in skin and pleura, a functional role for it in IL-4-induced eosinophil accumulation was evident only in skin. These findings suggest the existence of tissue-specific adhesive mechanisms in regulating leukocyte migration in vivo and demonstrate a dissociation between VCAM-1 expression and eosinophil accumulation.

Animals↗
PubMed1992

Differentiation and functional activity of human eosinophilic cells from an eosinophil HL-60 subline: response to recombinant hematopoietic growth factors.

We studied the effect of hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte [G]-CSF, interleukin (IL)-1, IL-3, IL-5, IL-6, and macrophage [M]-CSF) on differentiation and functional activity of human eosinophilic HL-60 cells (Eos-HL-60) and compared them with effects on parental HL-60 promyelocytic leukemia cells. Purified biosynthetic GM-CSF and IL-5 enhanced cell proliferation and induced eosinophilic differentiation in the eosinophilic subline in both liquid and agar cultures. IL-3 and IL-6 stimulated cell proliferation but had no effect on cell differentiation, whereas IL-1 and G-CSF affected neither differentiation nor proliferation of Eos-HL-60 cells under the conditions tested. GM-CSF-, IL-3-, and IL-5-treated Eos-HL-60 cells showed increased O2- production in response to phorbol esters (PMA), enhanced phagocytosis of Candida albicans, and release of the enzymes arylsulfatase, beta-glucuronidase and eosinophil peroxidase (EPO). The degranulation of eosinophils induced by GM-CSF, IL-5, and IL-3 may have relevance to the potential clinical toxicity of these hematopoietins, which also stimulate eosinophilopoiesis. G-CSF had no effect on enzyme release, oxidative metabolism, or phagocytic capacity of Eos-HL-60 cells. IL-5 did not affect proliferation, differentiation, or enzyme release in promyelocytic HL-60 cells. These results indicate the specificity of IL-5 for the eosinophil lineage, confirm the effects of GM-CSF and IL-3 on eosinophilopoiesis and mature eosinophil function in a model system, and indicate the absence of G-CSF and IL-1 stimulation of eosinophils. The Eos-HL-60 line is a useful model for studying human eosinophil responses to cytokines.

Candida albicans↗
PubMed2004

Interleukin-5, interleukin-3 and granulocyte-macrophage colony-stimulating factor prime actin-polymerization in human eosinophils: a study with hypodense and normodense eosinophils from patients with atopic dermatitis.

Characteristic features of atopic diseases (AD) are immigration and local activation of eosinophils. Reorganization of the cytoskeleton modulates the function of leukocytes and is a prerequisite for the motility response. In this work, the regulation of actin polymerization has been investigated by flow cytometry using NBD-phallacidin and right angle light scatter measurements in purified eosinophils isolated from patients with atopic dermatitis and normal individuals. Stimulation of eosinophils with chemotaxins such as complement fragment C5a (C5a), CC chemokine RANTES/ CCL5 and platelet activating factor (PAF) induced a reversible polymerization of actin. Normodense eosinophils purified from patients with AD showed a decreased chemotaxin-induced actin response as compared to normodense eosinophils from healthy subjects and hypodense eosinophils from patients. Stimulation of eosinophils with Th2-cytokines such as interleukin-3 (IL-3), interleukin-5 (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF) did not exert a significant effect on actin polymerization. However, pretreatment with IL-3, IL-5 or GM-CSF potentiated the chemotaxin-induced actin polymerization and graded the differential responsiveness between normodense and hypodense eosinophils. We demonstrate a different actin responsiveness in eosinophils from atopic patients and healthy subjects which could be overcome by modulating effects of Th2-cytokines.

Actins↗
PubMed1990

Murine eosinophils and IL-1: alpha IL-1 mRNA detection by in situ hybridization. Production and release of IL-1 from peritoneal eosinophils.

The presence of IL-1 mRNA in eosinophils from mice infected with larvae of the parasite Mesocestoides corti was investigated by in situ hybridization technique. S35 labeled cDNA probe for alpha IL-1, hybridized with mRNA in murine eosinophils and macrophages. After 6 h of LPS stimulation eosinophils were able to express mRNA in their cytoplasm. This expression was highly increased by the addition of indomethacine. The IL-1 mRNA expression in murine macrophages was higher than in eosinophils in LPS-stimulated cells. This difference was statistically significant, p less than 0.001. To test if eosinophils may produce and release IL-1 in the culture medium, we isolated these cells in a Percoll gradient. Cell preparations with a purity exceeding 94% were cultured with various stimuli and their supernatants were tested for IL-1 activity. Eosinophils produced 169.65 +/- 73 U/ml when stimulated with LPS (n = 14). A dose-dependent response was obtained when the eosinophils were in the presence of the calcium ionophore A23187. Controls were performed to rule out the contribution of the contaminating population on the thymocyte proliferating activity. They were also used to detect other possible causes of interference in the assay, such as leukotrienes or TNF. IL-1 in supernatants was also detected using a conversion assay such as EL-4 thymoma cells. IL-1 activity was first detected in culture supernatants 18 h later, maximal production being in the first 24 h. In accordance with our hybridization results, an increase in IL-1 activity was obtained when eosinophils were stimulated with LPS and treated with indomethacine. The factor had a molecular mass between 16 to 20 kDa that corresponded to the described for murine IL-1. Inasmuch as IL-1 is an important mediator of inflammatory reactions this IL may enhance the proinflammatory action of eosinophils.

Animals↗
PubMed1995

Intimate association of eosinophils to collagen bundles in eosinophilic myocarditis and ranitidine-induced hypersensitivity myocarditis.

BACKGROUND: Eosinophilic myocarditis is an inflammatory condition of the heart in which the infiltrate is composed predominately of eosinophils. DESIGN: We identified three cases of eosinophilic myocarditis in which the infiltrating eosinophils showed a remarkable intimate association with bundles of collagen. Two of the hearts examined were explants from heart transplant recipients with hypersensitivity myocarditis at the time of transplant and the third was from an autopsied patient with Churg-Strauss syndrome. These hearts were examined using light and electron microscopy. The cellular infiltrate in all three cases was characterized using immunoperoxidase stains with a panel including antibodies against myeloperoxidase, common leukocyte antigen (CD45), B lymphocytes (CD20), T lymphocytes (CD3), active-memory T lymphocytes (CD45RO), inactive T lymphocytes (CD45RA), and macrophages (CD68). RESULTS: Ultrastructural examination in all three cases confirmed the apposition of eosinophils to both large bundles of collagen and smaller aggregates of collagen fibrils. The eosinophils and the bundles of collagen stained strongly for myeloperoxidase, suggesting at least partial degranulation of the eosinophils. A KP-1 stain (CD68) revealed macrophages admixed with the eosinophils adjacent to the collagen bundles, and stains for CD45RA (naive lymphocytes) and CD45RO (memory T cells) showed an interstitial infiltrate of predominantly CD45RO-positive cells. Clinically, the cardiac decompensation of one of the transplant patients was most likely due to ranitidine-induced hypersensitivity myocarditis. CONCLUSIONS: These results suggest that some cases of eosinophilic myocarditis may be caused by the expression of novel antigens bound to collagen bundles. In one of the patients awaiting cardiac transplant, cardiac decompensation was temporally associated with ranitidine therapy, an agent not previously implicated as a cause of hypersensitivity myocarditis.

Adult↗
PubMed1995

Distinct immunohistochemical localization of IL-4 in human inflamed airway tissues. IL-4 is localized to eosinophils in vivo and is released by peripheral blood eosinophils.

Nasal polyposis and asthma are inflammatory conditions of the airways characterized by infiltration of activated inflammatory cells, particularly eosinophils. IL-4 is a multifunctional cytokine considered to play an important role in eosinophilic inflammation. We examined the cellular distribution of immunoreactive IL-4 in nasal polyps, as well as in the bronchial mucosa of both nonasthmatic control subjects (n = 6) and patients with well-characterized mild asthma (n = 6) subjected to a diluent or an allergen challenge. To determine eosinophilic contribution, tissue sections were counterstained with FITC after IL-4 immunostaining. No eosinophils were observed in the bronchial mucosa of nonasthmatic subjects. Nasal polyp tissues contained approximately 15 times more eosinophils per mm2 compared with bronchial tissues from asthmatics after a diluent challenge. Allergen challenge resulted in a marked increase in eosinophil density in bronchial tissues. A negligible number of cells immunostaining IL-4 was observed in bronchial tissues from nonasthmatic control subjects. The density of IL-4-positive cells in nasal polyp tissues was almost three times greater compared with asthmatics bronchial tissues after a diluent challenge. Approximately 90% of the IL-4-positive cells in bronchial tissues did not exhibit fluorescence after FITC counterstaining; in contrast, about 80% of the IL-4-positive cells in nasal polyp tissues did. We also show that peripheral blood eosinophils from allergic subjects express IL-4 mRNA by Northern blot analysis, particularly on stimulation with secretory IgA immune complexes. Finally, the supernatant of stimulated eosinophils contained approximately 50 pg/10(6) cells of IL-4 as determined by ELISA. These data demonstrate that eosinophils express the message and release IL-4 in vitro, and that these cells are the primary source of immunoreactive IL-4 in tissues undergoing chronic severe mucosal inflammation.

Adult↗
PubMed1996

Identification of surface molecules associated with physiologic activation of eosinophils. Application of whole-blood flow cytometry to eosinophils.

Activation is central to the eosinophil's functional role as an immune responder cell. To evaluate such activation in cells freshly isolated from peripheral blood, a method for whole-blood immunostaining and flow cytometry-based eosinophil selection was developed. Simultaneous comparison of purified eosinophils and whole-blood cells revealed significant differences in the levels of expression of various surface molecules, which suggested that the purification process activated the eosinophils. Subsequent analyses were conducted with the whole-blood assay. When eosinophils from helminth-infected persons (n = 18) were compared with those from normal individuals (n = 10), the early activation marker CD69 was found to be significantly increased (geometric mean (GM) = 4.3 vs. 1.0%, p = 0.04). The granulocyte activation marker CD66 was also up-regulated on eosinphils from helminth patients (GM = 53.3 vs. 31.0%, p = 0.044), as was the tetraspan family molecule CD81 (TAPA-1; GM = 79.4 vs. 48.2%, p = 0.02). Conversely, in vivo CD23 (FcepsilonRII) expression on eosinophils was decreased in the presence of parasitic infection (GM = 0.9 vs. 5.7%, p = 0.02). Expression of the eosinophil surface molecules CD69, CD81, and CD23 was significantly enhanced after cytokine stimulation in vitro with IL-3 or GM-CSF. In vivo, specific anthelmintic therapy resulted in decreased CD66 and CD25 expression (p < 0.05 compared with pretreatment) to levels approaching those seen in uninfected normal individuals. These findings indicate the dynamic nature of eosinophil surface molecules and demonstrate an important role for whole-blood staining in developing an understanding of the nature of eosinophil activation and of their role in inflammatory reactions to helminth parasites.

Anthelmintics↗
PubMed1998

Localization of eosinophil-derived neurotoxin and eosinophil cationic protein in neutrophilic leukocytes.

Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are generally regarded as eosinophil-specific proteins. We tested whether EDN and ECP are present in mature neutrophils. By indirect immunofluorescence, both eosinophils and neutrophils stained with antibodies to EDN and ECP. Lysates of purified (<0.1% eosinophil contamination) neutrophils contained EDN, 112+/-4 ng/10(6) cells, and ECP, 163+/-2 ng/10(6) cells, whereas eosinophil major basic protein (MBP) was not detectable. Electron microscopic examination of immunogold-labeled buffy coat cells stained with EDN antibody showed that EDN is localized to neutrophil granules. Finally, EDN mRNA was detected in lysates of highly purified neutrophils (0.001% eosinophil contamination) by the reverse transcription-polymerase chain reaction. We conclude that proteins that are either identical to or immunologically cross-reactive with EDN and ECP are present in neutrophils and that EDN is synthesized and localized to neutrophil granules. Thus, caution must be exercised in interpreting the presence of EDN and ECP as specific markers of eosinophil-associated inflammation in human disease.

Biopsy↗
PubMed1999

Major basic protein, but not eosinophil cationic protein or eosinophil protein X, is related to atopy in cystic fibrosis.

Increased eosinophil granule proteins have been described in serum and sputum samples of patients with cystic fibrosis (CF). It has been assumed that eosinophil degranulation is enhanced in atopic subjects - as in asthmatics. Since in CF no differences in eosinophil cationic protein (ECP), eosinophil protein X (EPX), and eosinophil peroxidase between atopic and nonatopic subjects have been detected, we investigated whether major basic protein (MBP) is increased in serum and sputum samples derived from atopic (n = 14) compared with nonatopic CF subjects (n = 26). In CF patients, high mean serum (sputum) levels of ECP 29.7 microg/l (2.7 mg/l), EPX 53.7 microg/l (7.9 mg/l), and MBP 984.6 microg/l but low sputum MBP levels (57.4 microg/l) were measured. In addition, in serum and in sputum samples, a significant correlation between MBP and ECP (P<0.03 and P<0.0001, respectively) or EPX (P<0.05 and P<0.0004, respectively) was detected. By subdivision of the patients into allergic and nonallergic subjects, significant differences were found for serum MBP values only(mean 1382.2 microg/l vs. 770.5 microg/l; P<0.0001), but not for ECP or EPX serum levels or for eosinophil proteins in sputum. Although no differences between atopic and nonatopic CF patients in ECP and EPX were found, serum MBP levels were higher in patients sensitized to inhalant allergens than in nonsensitized subjects. These results indicate differential release of eosinophil granule proteins in peripheral blood from eosinophils, and they also indicate that MBP in serum likely is to be a better discriminator of atopy in CF.

Adolescent↗
PubMed1996

Eosinophils and eosinophil-derived proteins in children with moderate asthma.

Laboratory parameters can contribute to the diagnosis of asthma, which is often a difficult procedure in paediatric patients. The aim of this study was to investigate the value of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) in the diagnosis of paediatric asthma. The number of eosinophils, serum ECP and EDN, and urinary EDN were determined in 22 children with stable, allergic asthma, aged 4-14 yrs, and in 17 age-matched healthy controls. Symptoms were monitored, the peak expiratory flow rate (PEFR) was recorded in the younger children, and lung function tests (forced expiratory volume in one second (FEV1) and the provocative concentration of histamine causing a 20% fall in FEV1 (PC20)) were performed in the older children. None of the asthmatic children had respiratory symptoms. PEFR was not significantly different in asthmatic children compared to controls. The FEV1 % predicted was significantly lower compared to controls. The number of eosinophils, serum ECP and EDN, and urinary EDN were significantly higher in asthmatic children compared with controls. After correction of serum ECP and EDN, and urinary EDN for the number of eosinophils, the differences between patients and controls disappeared. The nocturnal PEFR and the FEV1 were significantly related to urinary EDN. The results suggest that serum and urinary concentration of eosinophil-derived proteins can be determined instead of the number of eosinophils to support the diagnosis of asthma in childhood. The urinary concentration of eosinophil-derived neurotoxin can be especially valuable in young children, because in this age group quantification of lung function cannot be performed and blood sampling can be difficulty.

Adolescent↗