Survival Of Human Eosinophils Research Articles

ICAM-1 upregulation is not required for retinoic acid-induced human eosinophil survival

Active metabolites of vitamin A, retinoic acids (RAs), are known to play critical roles in mucosal immune responses and dramatically inhibit human eosinophil apoptosis, but the detailed mechanisms have not been elucidated. We previously screened for ICAM-1 (CD54) upregulation in RA-stimulated human eosinophils by gene microarray analysis. As ICAM-1 induction and activation were observed to have a role in maintenance of eosinophil survival, we tested the hypothesis that RAs prolong eosinophil survival through ICAM-1 outside-in signaling. Blood-derived isolated eosinophils cultured with 9-cis RA and all-trans RA showed significant upregulation of ICAM-1 mRNA and cell surface expression. TTNPB, a retinoic acid receptor agonist, also induced ICAM-1 expression, while HX630, a retinoid X receptor agonist, did not. Furthermore, an RAR antagonist, HX531, completely inhibited the effect of RAs. Upregulated ICAM-1 was associated with altered kinetics of Akt, ERK, and p38 MAP kinase phosphorylation through ICAM-1 cross-linking, but an ICAM-1-blocking antibody did not affect RA-mediated cell survival. These findings indicate that RAs induce functional ICAM-1 expression through RARs, but the induced ICAM-1 does not contribute to prolongation of eosinophil survival.

Physiologic concentrations of HMGB1 have no impact on cytokine-mediated eosinophil survival or chemotaxis in response to Eotaxin-2 (CCL24).

HMGB1 is an alarmin that can stimulate the innate immune system alone or in a complex with other inflammatory mediators. Given the recent interest in HMGB1 with respect to the pathogenesis of eosinophil-associated disorders, including asthmatic inflammation and chronic rhinosinusitis, we have explored the role of this mediator and in promoting eosinophil activation. HMGB1 receptors RAGE and TLR4 but not TLR2 were detected on freshly isolated human eosinophils from healthy donors. Physiologic and relevant pathophysiologic levels of biologically-active HMGB1 had no effect on survival of human eosinophils alone or in combination with pro-survival cytokines IL-5, IL-3, or GM-CSF, and increasing concentrations of HMGB1 had no impact on surface expression of RAGE, TLR2 or TLR4. Similarly, HMGB1 did not elicit chemotaxis of human eosinophils alone and had no effect in combination with the eosinophil chemotactic agent, eotaxin-2 (CCL24). However, surface expression of TLR2 and TLR4 increased in response to cell stress, notably on eosinophils that remain viable after 48 hours without IL-5. As such, HMGB1 signaling on eosinophils may be substantially more detailed, and may involve complex immunostimulatory pathways other than or in addition to those evaluated here.

Salbutamol delays human eosinophil apoptosis via a cAMP-dependent mechanism

Eosinophils play a major role in asthma. One described mechanism leading to the impaired clearance of these cells from the lung is the delay in their programmed cell death (apoptosis). β 2-Adrenoceptor agonists have been shown to prolong survival and delay apoptosis of eosinophils. The aim of the present study was to evaluate the mechanisms, especially the role of cAMP pathway, in the prolongation of human eosinophil survival by a selective β 2-agonist salbutamol. Isolated human peripheral blood eosinophils were cultured in the absence or presence of a β 2-agonist salbutamol and the indicated antagonists/inhibitors under sterile conditions. Apoptosis was measured by using the relative DNA fragmentation assay and Annexin-V binding. Salbutamol prolonged survival of human eosinophils and it was inhibited by a β-receptor antagonist propranolol and mimicked by cell-permeant cAMP analogues dibutyryl- and 8-bromo-cAMP. Pharmacological inhibitors of adenylyl cyclase (SQ-22,536) and protein kinase A (Rp-8-CPT-cAMPS) antagonized the effects of salbutamol. The survival-prolonging action of salbutamol was potentiated by a phosphodiesterase inhibitor rolipram (EC 50 for the salbutamol effect was 13.6 ± 4.0 and 8.1 ± 3.1 nM in the absence and presence of rolipram, respectively; p = 0.0142, n = 10). In contrast, inhibition of Ca 2+-activated K +-channels by apamin, charybdotoxin, iberiotoxin or paxilline did not affect the ability of salbutamol to prolong eosinophil survival. Taken together, the present results suggest that salbutamol at clinically relevant concentrations decreases apoptosis in human eosinophils by activating the cannonical β 2-receptor-adenylyl cyclase–cAMP-protein kinase A pathway.

A Novel IL-1 Family Cytokine, IL-33, Activates and Enhances Survival of Human Eosinophils

A Novel IL-1 Family Cytokine, IL-33, Activates and Enhances Survival of Human Eosinophils

Antieosinophilic Activity of Simendans

Simendans are novel agents used in the treatment of decompensated heart failure. They sensitize troponin C to calcium and open ATP-sensitive potassium channels and have been shown to reduce cardiac myocyte apoptosis. The aim of the present study was to evaluate whether simendans reduce pulmonary eosinophilia and regulate eosinophil apoptosis. Bronchoalveolar lavage (BAL) eosinophilia was evaluated in ovalbumin-sensitized mice. Effects of simendans on apoptosis in isolated human eosinophils were assessed by relative DNA fragmentation assay, annexin V-binding, and morphological analysis. Dextrosimendan [(+)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono]propanedinitrile] reduced ovalbumin-induced BAL-eosinophilia in sensitized mice. Levosimendan [(-)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile] and dextrosimendan reversed interleukin (IL)-5-afforded survival of human eosinophils by inducing apoptosis in vitro. Even high concentrations of IL-5 were not able to overcome the effect of dextrosimendan. Dextrosimendan further enhanced spontaneous apoptosis as well as that induced by CD95 ligation, without inducing primary necrosis. Dextrosimendan-induced DNA fragmentation was shown to be dependent on caspase and c-Jun NH2-terminal kinase activation, whereas extracellular signal-regulated kinase, p38 mitogen-activated kinase, and ATP-sensitive potassium channels seemed to play no role in its actions. Taken together, our results show that simendans possess antieosinophilic activity and may be useful for the treatment of eosinophilic inflammation.

Histamine reverses IL-5-afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine

Eosinophils are essential inflammatory cells in the pathogenesis of asthma and atopic conditions. Histamine, released from mast cells and basophils in response to allergen exposure, is a critical mediator in the allergic response. Histamine exerts its effects via four unequivocally characterized histamine receptors, H 1 - 4 . Several functions of eosinophils have previously been shown to be stimulated by histamine. However, its effects on eosinophil apoptosis are unknown. The aim of the present study was to resolve the effects of histamine on constitutive apoptosis of human eosinophils and on the survival-enhancing action of interleukin (IL)-5. Additional experiments were conducted to elucidate the histamine receptor(s) involved in any response seen and the associated signal transduction cascade. Human isolated peripheral blood eosinophils were cultured in the absence or presence of histamine, IL-5 and receptor antagonists/agonists or mediator inhibitors/analogues. Apoptosis was assessed by measuring the relative DNA content of propidium iodide (PI)-stained cells and the effects were confirmed by morphological analysis with bright field microscopy. Caspase activities were assessed by using commercial Caspase- Glo ® 3/7, 8 and 9 luminescence assays. Histamine ( 10 – 100 μ M ) partially reversed IL-5-induced human eosinophil survival by enhancing apoptosis as assessed by measuring the relative DNA content of PI-stained cells. This effect was not mediated through any of the known histamine receptors or through non-specific activation of 5-hydroxytryptamine receptors or α -adrenoceptors. Moreover, the reversal of IL-5-inhibited eosinophil apoptosis by histamine seemed not to utilize the conventional intracellular second-messenger pathways including cyclic AMP, protein kinase A or phospholipase C. Inhibition of caspase 6 and caspases 1, 10 or 12 reversed the effects of histamine but also inhibited apoptosis in general. In conclusion, the data presented herein indicate that histamine induces human eosinophil apoptosis in the presence of a survival-prolonging cytokine by a mechanism that does not apparently involve the activation of any of the currently known histamine receptor subtypes. The possibility exists that another, as yet unidentified, histamine receptor may exist in human eosinophils that regulates survival, although the participation of histamine receptor-independent mechanisms cannot be excluded.

Eosinophil Apoptosis Induced by Fungal Immunomodulatory Peptide- fve via Reducing IL-5α Receptor

Eosinophils are important effector cells in the pathogenesis of allergic bronchial asthma. Enhancement of eosinophil apoptosis has been considered to have therapeutic effect on allergic disease. Fungal immunomodulatory peptide (FIP)-fve has been reported to possess immunoprophylactic activities for allergic diseases. The purpose of this study was to investigate the modulation of FIP-fve on human eosinophil survival derived from allergic asthmatic patients. Eosinophils were obtained from allergic asthmatic patients and purified with the use of density gradients and immunomagnetic beads negative selection. Apoptosis was assessed by annexin V and propidium iodide. The apoptotic signal protein, CD95 and IL-5 receptor expression were assessed by Western blot and flow cytometric analysis. When the eosinophils were treated with FIP-fve in the presence of IL-5, IL-5-enhanced eosinophil survival diminished. FIP-fve could reduce IL-5-mediated survival of eosinophils and decrease IL-5Ralpha expression. In the presence of FIP-fve, CD95 expression was upregulated and Bcl-xL and pro-caspase 3 expression were downregulated in cultured eosinophils. The results suggest that FIP-fve can inhibit IL-5-mediated survival of eosinophils through the modulation of cytokine receptor expression and apoptotic signal protein production. The modulatory effect of FIP-fve on eosinophil apoptosis in vitro indicates that it may have some therapeutic effect on eosinophil-related allergic inflammation in vivo.

Antieosinophilic Activity of Orazipone

Orazipone is a novel sulfhydryl-reactive compound that has been previously shown to reduce lung eosinophilia in guinea pigs and rats and to inhibit degranulation in mast cells and cytokine production in monocytes and T-cells. However, the effects of orazipone on granulocyte longevity are unknown. Orazipone and its derivative 3-(4-chloro-3-nitro-benzylidene)-pentane-2,4-dione (OR-2370) reversed interleukin-5-afforded survival of human eosinophils by inducing apoptosis. In contrast, orazipone did not affect granulocyte macrophage-colony-stimulating factor-induced survival of human neutrophils. The effect of orazipone on eosinophil apoptosis is different from that of glucocorticoids in that even high con-centrations of interleukin-5 were not able to overcome the effect of orazipone. Orazipone further enhanced spontaneous apoptosis as well as that induced by CD95 ligation without inducing primary necrosis. OR-2370-induced DNA fragmentation was shown to be dependent on caspases 3 and 6 and c-jun-N-terminal kinase, whereas extracellular regulated kinase, p38 mitogen-activated protein kinase, and phosphatidylinositol 3-kinase as well as caspases 4, 8, and 9 seem not to mediate its actions. Our results suggest that orazipone and its derivative OR-2370 possess strong antieosinophilic activity and thus may have anti-inflammatory efficacy in the treatment of asthma and/or allergic conditions.

CpG Oligodeoxynucleotide Prolongs Human Eosinophil Survival through Activation of B Cells or Plasmacytoid Dendritic Cells in vitro

CpG Oligodeoxynucleotide Prolongs Human Eosinophil Survival through Activation of B Cells or Plasmacytoid Dendritic Cells in vitro

CpG oligodeoxynucleotide prolongs human eosinophil survival through activation of NF-κB

Rationale Oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) are known to exert a strong adjuvant effect on Th1 immune responses via TLR9, and are thought to be potential therapeutic agents for patients with allergic diseases. However, their effects on human eosinophils are still unclear. Methods To determine the effect of CpG-ODN on human eosinophils, eosinophils were purified from peripheral blood of healthy or slightly allergic donors. Expression of TLR9 was assessed by RT-PCR. Eosinophils were suspended in PRMI1640 supplemented with 10% FCS at a cell density of 1 × 10 6/ml, and cultured in the presence or absence of synthetic CpG-ODN2006 (CpG-B), CpG-ODN2216 (CpG-A) or their GpC control ODNs for 24 hours. Eosinophil survival was measured with FITC-conjugated Annexin-V and propidium iodide by FACS. EDN concentration and cytokine levels in the supernatant were quantified by ELISA. Results Eosinophils constitutively expressed mRNA for TLR9. CpG-ODN2006 significantly prolonged eosinophil survival, whereas GpC control did not (at 2 μg/ml ODNs, Annexin-V +% (mean ± SEM) for CpG-ODN2006, CpG-ODN2216 and GpC-ODN was 36.5 ± 4.2%∗, 56.4 ± 5.8% and 60.1 ± 2.2%, respectively, ∗p=0.0001). Prolongation of eosinophil survival was inhibited by two NF-κB inhibitors - MG132 and PDTC - and was partially inhibited by neutralizing mAb against GM-CSF. Neither EDN release nor cytokine production (IL-8 or M-CSF) was observed in the supernatant 24 hours after stimulation with CpG-ODNs. Conclusions These results strongly suggest that eosinophils express functional TLR9. Stimulation with CpG-ODN2006 promotes eosinophil survival through activation of NF-κB, and in part through GM-CSF-autocrine, but does not induce degranulation.

Hydrogen Peroxide Reverses IL-5 Afforded Eosinophil Survival and Promotes Constitutive Human Eosinophil Apoptosis

Background: Eosinophils play a central role in the induction and perpetuation of allergic inflammatory responses. The present study was performed to investigate the effects of reactive oxygen intermediates on constitutive apoptosis as well as on interleukin (IL)-5 afforded human eosinophil survival. Methods: Peripheral blood eosinophils were isolated by CD16-negative selection to >99% purity and were cultured for 48 h. The number of apoptotic eosinophils in the culture was assessed by flow cytometric analysis of relative DNA content in propidium-iodide-stained cells, annexin-V binding or by morphological analysis. Apoptosis was confirmed by the appearance of a typical ladder pattern in the DNA fragmentation assay by agarose gel electrophoresis. Results: Exogenous H₂O₂ reversed IL-5-afforded eosinophil survival by inducing apoptosis. Constitutive eosinophil apoptosis was inhibited by a reduction of intracellular levels of H₂O₂ by catalase. Exogenous H₂O₂ increased the rate of constitutive apoptosis. Conclusions: Our results suggest that H₂O₂ may play a role in the downregulation of eosinophilic inflammation by inducing eosinophil apoptosis.

Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils

AbstractInterleukin-9 (IL-9) has been implicated in the pathogenesis of allergic disorders. To examine the interaction between IL-9 and eosinophils, we evaluated mature peripheral blood eosinophils for their expression of the specific α-subunit of the IL-9 receptor (IL-9R–α). The expression of IL-9R–α by human eosinophils was detected at the messenger RNA (mRNA) and protein levels by reverse transcriptase–polymerase chain reaction (RT-PCR), flow cytometry, and immunocytochemical analysis, respectively. Functional analyses demonstrated that recombinant human (rh)IL-9 inhibited in vitro peripheral blood human eosinophil apoptosis in a concentration-dependent manner. We then examined the role of IL-9 in eosinophil differentiation using the human cord blood CD34+cells and human promyelocytic leukemia cells (HL-60). The addition of IL-9 to CD34+ cells cultured in IL-3 and IL-5 enhanced eosinophil development, and IL-9 alone induced the expression of IL-5R–α. IL-9 also up-regulated the IL-5R–α chain cell surface expression during terminal eosinophil differentiation of the HL-60 cell line. Our findings suggest that IL-9 may potentiate in vivo eosinophil function by increasing their survival and IL-5–mediated differentiation and maturation. Taken together, these results suggest a mechanism by which IL-9 potentiates airway and tissue eosinophilia.

Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils

Interleukin-9 (IL-9) has been implicated in the pathogenesis of allergic disorders. To examine the interaction between IL-9 and eosinophils, we evaluated mature peripheral blood eosinophils for their expression of the specific alpha-subunit of the IL-9 receptor (IL-9R-alpha). The expression of IL-9R-alpha by human eosinophils was detected at the messenger RNA (mRNA) and protein levels by reverse transcriptase-polymerase chain reaction (RT-PCR), flow cytometry, and immunocytochemical analysis, respectively. Functional analyses demonstrated that recombinant human (rh)IL-9 inhibited in vitro peripheral blood human eosinophil apoptosis in a concentration-dependent manner. We then examined the role of IL-9 in eosinophil differentiation using the human cord blood CD34(+) cells and human promyelocytic leukemia cells (HL-60). The addition of IL-9 to CD34(+) cells cultured in IL-3 and IL-5 enhanced eosinophil development, and IL-9 alone induced the expression of IL-5R-alpha. IL-9 also up-regulated the IL-5R-alpha chain cell surface expression during terminal eosinophil differentiation of the HL-60 cell line. Our findings suggest that IL-9 may potentiate in vivo eosinophil function by increasing their survival and IL-5-mediated differentiation and maturation. Taken together, these results suggest a mechanism by which IL-9 potentiates airway and tissue eosinophilia.

761 Interleukin-9 enhances IL-5 receptor expression, differentiation and survival of human eosinophils

761 Interleukin-9 enhances IL-5 receptor expression, differentiation and survival of human eosinophils

Engagement of α4β7 Integrins by Monoclonal Antibodies or Ligands Enhances Survival of Human Eosinophils In Vitro

AbstractAsthma is characterized by an airway inflammatory infiltrate that is rich in eosinophilic leukocytes. Cellular fibronectin and VCAM-1, ligands for α4 integrins, are enriched in the fluid of airways of allergic patients subjected to Ag challenge. We therefore hypothesized that ligands of α4 integrins can promote eosinophil survival independent of cell adhesion. Cellular fibronectin and VCAM-1 increased viability of human peripheral blood eosinophil in a dose- and time-dependant manner whether the ligand was coated on the culture well or added to the medium at the beginning of the assay. Eosinophils cultured with cellular fibronectin were not adherent to the bottom of culture wells after 3 days. Treatment with mAb Fib 30 to β7, but not mAb P4C10 or TS2/16 to β1, increased eosinophil survival. The increased survival of eosinophils incubated with Fib 30 was blocked by Fab fragments of another anti-β7 mAb, Fib 504. Eosinophils incubated with soluble cellular fibronectin or mAb Fib 30 for 6 h demonstrated a higher level of GM-CSF mRNA than eosinophils incubated with medium alone. Addition of neutralizing mAb to GM-CSF during incubation, but not mAbs to IL-3 or IL-5, reduced the enhancement of eosinophil survival by soluble cellular fibronectin or mAb Fib 30 to control levels. Thus, viability of eosinophils incubated with cellular fibronectin or VCAM-1 is due to engagement, probably followed by cross-linking, of α4β7 by soluble ligand (or mAb) that stimulates autocrine production of GM-CSF and promotes eosinophil survival.

Ligation of FcγRII (CD32) Pivotally Regulates Survival of Human Eosinophils

Abstract The low-affinity IgG Fc receptor, FcγRII (CD32), mediates various effector functions of lymphoid and myeloid cells and is the major IgG Fc receptor expressed by human eosinophils. We investigated whether FcγRII regulates both cell survival and death of human eosinophils. When cultured in vitro without growth factors, most eosinophils undergo apoptosis within 96 h. Ligation of FcγRII by anti-CD32 mAb in solution inhibited eosinophil apoptosis and prolonged survival in the absence of growth factors. Cross-linking of human IgG bound to FcγRII by anti-human IgG Ab or of unoccupied FcγRII by aggregated human IgG also prolonged eosinophil survival. The enhanced survival with anti-CD32 mAb was inhibited by anti-granulocyte-macrophage-CSF (GM-CSF) mAb, suggesting that autocrine production of GM-CSF by eosinophils mediated survival. In fact, mRNA for GM-CSF was detected in eosinophils cultured with anti-CD32 mAb. In contrast to mAb or ligands in solution, anti-CD32 mAb or human IgG, when immobilized onto tissue culture plates, facilitated eosinophil cell death even in the presence of IL-5. Cell death induced by these immobilized ligands was accompanied by DNA fragmentation and was inhibited when eosinophil β2 integrin was blocked by anti-CD18 mAb, suggesting that β2 integrins play a key role in initiating eosinophil apoptosis. Thus, FcγRII may pivotally regulate both survival and death of eosinophils, depending on the manner of receptor ligation and β2 integrin involvement. Moreover, the FcγRII could provide a novel mechanism to control the number of eosinophils at inflammation sites in human diseases.

Effects of saiboku-to on the survival of human eosinophils.

In recent years, bronchial asthma has come to be regarded as a chronic inflammatory disease of the respiratory tract, with mast cells, lymphocytes and eosinophils playing important roles in its pathogenesis. Proteins contained in eosinophil granules, especially major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPO), can cause tissue injury. When stimulated, eosinophils release mediators such as leukotriene C4 (LTC4) and platelet activating factors (PAF). Thus, they are recognized as effector cells that are actively involved in the development of allergic inflammation. In this study, eosinophils from healthy volunteers were used to investigate the effects of Saiboku-to on eosinophils whose survival had been prolonged through stimulation with eosinophil-activating cytokines such as interleukin (IL)-3, IL-5 and granulocyte macrophage colony stimulating factors (GM-CSF). As a result, the cytokine-enhanced survival of eosinophils was significantly shortened by the addition of Saiboku-to. These findings suggest that Saiboku-to has the potential to inhibit allergic responses by directly affecting eosinophils which are related to allergic inflammation.

Effects of Intracellular Cyclic AMP Modulators on Human Eosinophil Survival, Degranulation and CD11b Expression

Background: Brochial asthma is characterized by infiltration of inflammatory cells such as lymphocytes and eosinophils. Theophylline is one of the most widely used drugs in the therapy of bronchial asthma, and phosphodiesterase (PDE) inhibition is thought to be an important mechanism of its anti–inflammatory actions. However, the detailed effects of PDE inhibition on eosinophils still remain unclear. Methods: Eosinophils in peripheral blood obtained from normal subjects and patients with mild off–season allergic rhinitis were purified using CD16 negative selection. The following effects of theophylline (nonselective PDE inhibitor), KF19514 (selective PDE IV inhibitor), mirlinone (selective PDE III inhibitor), procaterol (β2–adrenoceptor agonist) and N⁶, 2′–O–dibutyryladenosine 3′5′–cyclic monophosphate (dB–cAMP; AMP analogue) on eosinophils were examined: (1) survival in the presence of interleukin–5, (2) degranulation by granulocyte/macrophage colony–stimulating factor (GM–CSF) or platelet–activating factor (PAF), (3) CD11b expression under GM–CSF or PAF stimulation and (4) intracellular cAMP level. Results: Eosinophil survival was inhibited by theophilline, KF19514 or procaterol. GM–CSF– or PAF–induced degranulation was inhibited by theophylline, KF19514, procaterol or dB–cAMP. CD11b up–regulation by PAF was inhibited by theophylline, KF19514 or dB–cAMP, while GM–CSF–stimulated CD11b up–regulation was not significantly inhibited by any of the drugs tested. The levels of intracellular cAMP were increased by theophylline, KF19514 and procaterol. Conclusions: Intracellular cAMP is an important factor in the regulation of eosinophil biological functions. PDE IV inhibitors and β₂–agonists are suggested to be useful for the treatment of bronchial asthma through inhibition of eosinophil effector function.

An Interleukin 5 Mutant Distinguishes between Two Functional Responses in Human Eosinophils

Interleukin 5 (IL-5) is the key cytokine involved in regulating the production and many of the specialized functions of mature eosinophils including priming, adhesion, and survival. We have generated a point mutant of human IL-5, IL-5 (E12K), which is devoid of agonist activity in both a TF-1 cell proliferation assay and a human eosinophil adhesion assay. However, IL-5 (E12K) is a potent and specific antagonist of both these IL-5-dependent functional responses. In both receptor binding and cross-linking studies the wild-type and IL-5 (E12K) mutant exhibit virtually identical properties. This mutant protein was unable to stimulate tyrosine phosphorylation in human eosinophils, and blocked the phosphorylation stimulated by IL-5. In contrast, IL-5 (E12K) is a full agonist in a human eosinophil survival assay, although with reduced potency compared to the wild-type protein. This IL-5 mutant enables us to clearly distinguish between two IL-5-dependent functional responses and reveals distinct mechanisms of receptor/cellular activation.

Mechanisms of human eosinophil survival and apoptosis

Mechanisms of human eosinophil survival and apoptosis