scholarly journals Eosinophils express a functional receptor for interferon alpha: inhibitory role of interferon alpha on the release of mediators

Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2354-2360 ◽  
Author(s):  
D Aldebert ◽  
B Lamkhioued ◽  
C Desaint ◽  
AS Gounni ◽  
M Goldman ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Hypereosinophilic Syndrome ◽  
Eosinophil Cationic Protein ◽  
Dependent Manner ◽  
Cationic Protein ◽  
Interleukin 5 ◽  
Beneficial Effects ◽  
Eosinophil Granule ◽  
Eosinophilic Disorders ◽  
Functional Receptor

Recent reports describe the beneficial use of alpha interferon (IFNalpha) for the treatment of idiopathic hypereosinophilic syndrome (HES) unresponsive to conventional therapy. A clinical improvement associated with a rapid decrease of peripheral blood eosinophilia suggested possible direct effects of IFNalpha on eosinophils through the presence of IFNalpha receptors (IFNalphaR). Reverse transcriptase- polymerase chain reaction (RT-PCR) and cytochemistry were used respectively to detect the presence and define the distribution of IFNalphaR on enriched eosinophil preparations purified from blood cells. IFNalphaR was found on eosinophils collected from patients with various eosinophilic disorders. In addition, IFNalpha inhibited the release of eosinophil granule proteins such as eosinophil cationic protein (ECP), neurotoxin (EDN, or interleukin-5 (IL-5). Moreover, antiparasite cytotoxicity was also strongly reduced in a dose-dependent manner by IFNalpha. These results provide the first evidence that human eosinophils express a functional receptor for IFNalpha and represent a potential basis for the beneficial effects of IFNalpha in patients with hypereosinophilic syndromes.

scholarly journals Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1553-1560 ◽  
Author(s):  
P Desreumaux ◽  
A Janin ◽  
S Dubucquoi ◽  
MC Copin ◽  
G Torpier ◽  
...  
Keyword(s):  
Heart Diseases ◽  
Elevated Serum ◽  
Eosinophil Cationic Protein ◽  
Eosinophil Infiltration ◽  
Cationic Protein ◽  
Interleukin 5 ◽  
Eosinophil Granule Proteins ◽  
Eosinophil Activation ◽  
Granule Proteins ◽  
Eosinophil Granule

Abstract Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.

scholarly journals Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1553-1560 ◽  
Author(s):  
P Desreumaux ◽  
A Janin ◽  
S Dubucquoi ◽  
MC Copin ◽  
G Torpier ◽  
...  
Keyword(s):  
Heart Diseases ◽  
Elevated Serum ◽  
Eosinophil Cationic Protein ◽  
Eosinophil Infiltration ◽  
Cationic Protein ◽  
Interleukin 5 ◽  
Eosinophil Granule Proteins ◽  
Eosinophil Activation ◽  
Granule Proteins ◽  
Eosinophil Granule

Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.

scholarly journals Effects of human eosinophil granule-derived cationic proteins on C-fiber afferents in the rat lung

2001 ◽  
Vol 91 (3) ◽  
pp. 1318-1326 ◽  
Author(s):  
Lu-Yuan Lee ◽  
Qihai Gu ◽  
Gerald J. Gleich
Keyword(s):  
Eosinophil Cationic Protein ◽  
Eosinophil Infiltration ◽  
Cationic Protein ◽  
Human Eosinophil ◽  
Lung Inflation ◽  
Cationic Proteins ◽  
C Fibers ◽  
Arterial Blood ◽  
C Fiber ◽  
Eosinophil Granule

Experiments were performed to test the hypothesis that human eosinophil granule-derived cationic proteins stimulate vagal C-fiber afferents in the lungs and elicit pulmonary chemoreflex responses in anesthetized Sprague-Dawley rats. Intratracheal instillation of eosinophil cationic protein (ECP; 1–2 mg/ml, 0.1 ml) consistently induced an irregular breathing pattern, characterized by tachypnea (change in breathing frequency of 44.7%) and small unstable tidal volume (Vt). The tachypnea, accompanied by decreased heart rate and arterial blood pressure, started within 30 s after the delivery of ECP and lasted for >30 min. These ECP-induced cardiorespiratory responses were completely prevented by perineural capsaicin treatment of both cervical vagi, which selectively blocked C-fiber conduction, suggesting the involvement of these afferents. Indeed, direct recording of single-unit activities of pulmonary C-fibers further demonstrated that the same dose of ECP evoked a pronounced and sustained (>30-min) stimulatory effect on pulmonary C-fibers. Furthermore, the sensitivity of these afferents to lung inflation was also markedly elevated after the ECP instillation, whereas the vehicle of ECP administered in the same manner had no effect. Other types of eosinophil granule cationic proteins, such as major basic protein and eosinophil peroxidase, induced very similar respiratory and cardiovascular reflex responses. In conclusion, these results show that eosinophil granule-derived cationic proteins induce a distinct stimulatory effect on vagal pulmonary C-fiber endings, which may play an important role in the airway hyperresponsiveness associated with eosinophil infiltration in the airways.

scholarly journals Differentiating the endotypes in allergic rhinitis

2021 ◽  
Vol 36 (2) ◽  
pp. 92-97
Author(s):  
A. V. Klimov ◽  
Z. V. Salahutdinova ◽  
N. A. Pronina ◽  
G. A. Kuznetsov
Keyword(s):  
Allergic Rhinitis ◽  
Eosinophil Cationic Protein ◽  
Skin Tests ◽  
Research Trend ◽  
General Group ◽  
Cationic Protein ◽  
Total Ige ◽  
Interleukin 5 ◽  
Local Allergic Rhinitis ◽  
History Of

Aim. The aim of the study was to differentiate the endotypes in allergic rhinitis by key allergy markers in a mixed group of patients.Material and Methods. The study comprised a total of 48 patients, men and women, aged 18-60 years suffering from three endotypes of allergic rhinitis including the classic, local, and dual allergic rhinitis. The standard diagnostics of allergic rhinitis included taking a history of allergies, family history of allergic disease, video rhinoscopy, serum total IgE level assessment, allergy skin tests to house dust mite and pollen allergens, and study of eosinophilic inflammation parameters (eosinophil cationic protein, interleukin-5 (IL5), and eosinophil counts in blood and nasal secretion).Results. Based on total IgE level, the general group of patients was divided to two subgroups: subgroup 1 comprised patients with high IgE level (n = 22); subgroup 2 comprised patients with low IgE level (n = 26). Most of patients in these groups had contradictory results of allergy skin tests i.e. positive allergy skin test results in case of high IgE level (group 1) and vice versa. Cluster analysis-based exminations of general group allowed to categorize three subgroups of patients: patients with classic allergic rhinitis (n = 22), local allergic rhinitis (n = 22), and dual allergic rhinitis (n = 4). Besides, an increased rate of anxiety disorder was found in patients with local allergic rhinitis (p < 0.001).Conclusion. The obtained data showed promise for a new research trend in studying allergic rhinitis endotypes, namely: investigation of neuroimmune relationships in allergic tolerance disruption in the presence of this pathology.

Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 1911-1917 ◽  
Author(s):  
Gita T. Kampen ◽  
Susan Stafford ◽  
Tetsuya Adachi ◽  
Tan Jinquan ◽  
Sha Quan ◽  
...  
Keyword(s):  
Map Kinases ◽  
Inflammatory Diseases ◽  
Eosinophil Cationic Protein ◽  
Dependent Manner ◽  
Cationic Protein ◽  
Concentration Dependent Manner ◽  
P38 Inhibitor ◽  
Mitogen Activated Protein ◽  
Integral Role ◽  
Functional Relevance

Abstract Eotaxin and other CC chemokines acting via CC chemokine receptor-3 (CCR3) are believed to play an integral role in the development of eosinophilic inflammation in asthma and allergic inflammatory diseases. However, little is known about the intracellular events following agonist binding to CCR3 and the relationship of these events to the functional response of the cell. The objectives of this study were to investigate CCR3-mediated activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase-2 (ERK2), p38, and c-jun N-terminal kinase (JNK) in eosinophils and to assess the requirement for MAP kinases in eotaxin-induced eosinophil cationic protein (ECP) release and chemotaxis. MAP kinase activation was studied in eotaxin-stimulated eosinophils (more than 97% purity) by Western blotting and immune-complex kinase assays. ECP release was measured by radioimmunoassay. Chemotaxis was assessed using Boyden microchambers. Eotaxin (10−11 to 10−7 mol/L) induced concentration-dependent phosphorylation of ERK2 and p38. Phosphorylation was detectable after 30 seconds, peaked at about 1 minute, and returned to baseline after 2 to 5 minutes. Phosphorylation of JNK above baseline could not be detected. The kinase activity of ERK2 and p38 paralleled phosphorylation. PD980 59, an inhibitor of the ERK2-activating enzyme MEK (MAP ERK kinase), blocked phosphorylation of ERK2 in a concentration-dependent manner. The functional relevance of ERK2 and p38 was studied using PD98 059 and the p38 inhibitor SB202 190. PD98 059 and SB202 190 both caused inhibition of eotaxin-induced ECP release and chemotaxis. We conclude that eotaxin induces a rapid concentration-dependent activation of ERK2 and p38 in eosinophils and that the activation of these MAP kinases is required for eotaxin-stimulated degranulation and directed locomotion.

scholarly journals Lyn, Jak2, and Raf-1 Kinases Are Critical for the Antiapoptotic Effect of Interleukin 5, whereas only Raf-1 Kinase Is Essential for Eosinophil Activation and Degranulation

1998 ◽  
Vol 188 (3) ◽  
pp. 421-429 ◽  
Author(s):  
Konrad Pazdrak ◽  
Barbara Olszewska-Pazdrak ◽  
Susan Stafford ◽  
Roberto P. Garofalo ◽  
Rafeul Alam
Keyword(s):  
Tyrosine Kinases ◽  
Eosinophil Cationic Protein ◽  
Signaling Molecules ◽  
Therapeutic Approaches ◽  
Cationic Protein ◽  
Interleukin 5 ◽  
Eosinophil Survival ◽  
Eosinophil Activation ◽  
Functional Relevance ◽  
Eosinophil Apoptosis

Interleukin (IL)-5 has been shown to activate many signaling molecules in eosinophils, but their functional relevance remains unknown. We have examined the functional relevance of Lyn, Jak2, and Raf-1 kinases in eosinophil survival, upregulation of adhesion molecules and degranulation. To this goal we used Lyn and Raf-1 antisense (AS) oligodeoxynucleotides (ODN) to inhibit the expression of these proteins and tyrphostin AG490 to specifically block the activation of Jak2. We have demonstrated that all three kinases are important for IL-5– induced suppression of eosinophil apoptosis. However, Lyn and Jak2 tyrosine kinases are not important for the upregulation of CD11b and the secretion of eosinophil cationic protein. In contrast, Raf-1 kinase is critical for both these functions. This is the first identification of specific signaling molecules responsible for three important functions of eosinophils. We have established a central role for Raf-1 kinase in regulating eosinophil survival, expression of β2 integrins and degranulation. Further, there appears to be a dissociation between two receptor-associated tyrosine kinases, i.e., Lyn and Jak2, and the activation of Raf-1 kinase. The delineation of the functional relevance of signaling molecules will help design therapeutic approaches targeting specific eosinophil function.

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