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

Abstract

FcεRI 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 FcεRI by blood eosinophils from hypereosinophilic patients and normal donors. The number of unoccupied receptors corresponded to ∼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 FcεRI expression by mouse eosinophils has hampered further studies. To overcome this fact and experimentally confirm our findings on human eosinophils, we engineered IL-5 × hFcεRIα double-transgenic mice, whose bone marrow, blood, spleen, and peritoneal eosinophils expressed FcεRI 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 FcεRI engagement. Thus, comparative analysis of cells from patients and from a relevant animal model allowed us to clearly demonstrate that FcεRI-mediated eosinophil activation leads to IL-10 secretion. Through FcεRI expression, these cells are able to contribute to both the regulation of the immune response and to its effector mechanisms.

IgE-Antibody-Dependent Immunotherapy of Solid Tumors: Cytotoxic and Phagocytic Mechanisms of Eradication of Ovarian Cancer Cells

“…In the latter specimens, eosinophil degranulation was less common and tumor cells appeared more brightly fluorescent and viable. As previously reported, we found eosinophils to express low levels of the FcRI receptor but not CD23 (results not shown) (47). These results support a role for FcRI in IgE ADCC of tumor cells by eosinophils as well as monocytes.…”

“…In this study, we show for the first time that a tumor Ag-specific Ab can direct eosinophils to kill tumor cells by ADCC. As observed with monocytes, and consistent with the expression of low levels of FcRI on the surface of eosinophils (47), this IgE receptor on eosinophils appears to mediate MOv18-dependent cytotoxicity of tumor cells. Engagement of IgE Abs on the surface of eosinophils triggers the release of inflammatory and cytotoxic mediators, such as eosinophil peroxidase and major basic protein (63), which may contribute to tumor cell death.…”

“…PBMCs were depleted of monocytes by incubation with anti-CD14-coated immunomagnetic beads to label monocytes, followed by the removal of labeled monocytes using a VarioMACS immunomagnetic device (Miltenyi Biotec) according to the manufacturer's instructions. Eosinophils were isolated to Ͼ95% purity by Percoll gradient centrifugation (density 1.082 g/ml) (GE Healthcare) followed by immunomagnetic separation with anti-CD16-coated immunomagnetic beads as previously described (47), and used for assays immediately. All work was performed with the approval of the Guy's Research Ethics Committee and with the volunteers' written informed consent.…”

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

“…The authors concluded that eosinophils selectively release mediators as a result of stimulation of membrane receptors for immunoglobulins according to their type. Kayaba et al [82] demonstrated that the IgE-mediated ac-www.pneumonologia.viamedica.pl [79] did not observe any significant biological effect (degranulation or production of oxygen radicals or release of leukotriene C4) after the FceRI stimulation on eosinophils.…”

A breakthrough in probiotics: Clostridium butyricum regulates gut homeostasis and anti-inflammatory response in inflammatory bowel disease

“…Many IL-10-expressing cell subsets have been found, such as T h 1 cells [103][104][105], Foxp3 ? T reg cells [106][107][108], Foxp3 -T reg cells [109], B cells [110,111], macrophages [112][113][114], dendritic cells [115][116][117], neutrophils [118], and eosinophils [119]. IL-10-deficient mice are well established as a genetic model for IBD.…”