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.

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 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.

Effect of Pretreatment with Ketotifen on Pollinosis: Correlation with Eosinophil Cationic Protein

1994 ◽  
Vol 8 (1) ◽  
pp. 49-54 ◽  
Author(s):  
Shigeharu Fujieda ◽  
Ichiro Noda ◽  
Chizuru Sugimoto ◽  
Shigehito Mori ◽  
Hitoshi Saito
Keyword(s):  
Pollen Season ◽  
Eosinophil Cationic Protein ◽  
Pollen Allergy ◽  
Nasal Discharge ◽  
Cationic Protein ◽  
Nasal Sample ◽  
Symptom Scores ◽  
Eosinophil Activation

In this study, we examined the effect of pretreatment with ketotifen on pollinosis, and correlations with the concentration of ECP in nasal discharge and the existence of eosinophils in nasal smear. Ketotifen was prophylactically administered to 74 patients with pollen allergy, and the treatment continued to the end of pollen season. An additional 25 patients with the same allergy commenced ketotifen treatment during the pollen season. The results showed that pretreatment with ketotifen reduced symptom scores during the pollen season, but did not suppress the increase in ECP concentration and eosinophil influx into the nasal sample. We suggest that pretreatment with ketotifen is useful for the treatment of pollinosis, and its effects may not be the result of suppression of eosinophil activation.

Effect of Immunotherapy on Serum Levels of Eosinophil Cationic Protein in Perennial Allergic Rhinitis

1997 ◽  
Vol 106 (10) ◽  
pp. 848-853 ◽  
Author(s):  
Yoshiaki Nakai ◽  
Hirokazu Sakamoto ◽  
Yoshihiro Ohashi ◽  
Yasushi Kakinoki ◽  
Akifumi Kato ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Clinical Effect ◽  
Eosinophil Cationic Protein ◽  
Serum Levels ◽  
Untreated Group ◽  
Perennial Allergic Rhinitis ◽  
Cationic Protein ◽  
The Mean ◽  
Eosinophil Activation ◽  
Rate Of Activation

Eosinophil cationic protein (ECP) levels in the serum of clotted blood could reflect the rate of activation of circulating eosinophils. We investigated the serum ECP levels in patients with perennial allergic rhinitis, with special reference to the effect of immunotherapy on the serum ECP levels. Serum ECP levels in untreated patients with perennial allergic rhinitis are significantly higher than those of nonatopic volunteers. Therefore, this elevation in the untreated patients represents an ongoing inflammation occurring in allergic rhinitis. The mean serum ECP level of a 1-year immunotherapy group was significantly higher than that of the nonatopic group, and was not different from that of the untreated group. In contrast, the mean serum ECP level in patients who had more than 2 years of immunotherapy was significantly lower than that of the untreated group, and was not different from that of the nonatopic group. Additionally, serum ECP levels were significantly correlated with the duration of immunotherapy. These findings suggest that activation of circulating eosinophils decreases gradually during immunotherapy, but this inhibition becomes apparent only after 2 years of immunotherapy. The control of circulating eosinophil activation might be one of the important working mechanisms behind the clinical effect of immunotherapy.

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