Role of FcγRI in Antigen-Dependent Eosinophil Activation in Patients With Allergic Rhinitis

Abstract

Background The eosinophil (Eo) activation is a crucial factor evoking allergic rhinitis (AR) attacks; factors; the mechanism of triggering Eo activation remains to be further investigated. The interaction of antigen (Ag) and antibody plays a critical role in evoking allergy attacks. This study aims to elucidate the role of FcγRI, the high affinity receptor of IgG, in the Ag-mediated Eo activation. Methods Nasal lavage fluids (NLF) were collected from AR patients and healthy control (HC) subjects. Eos were isolated by flow cytometry cell sorting and analyzed by pertinent immunological approaches. Results Eos composed more than 60% of the cellular components in AR NLF. Exposure to specific Ags (sAgs) in the culture triggered Eos to release inflammatory mediators. High levels of FcγRI were detected on the surface of AR NLF Eos. Exposure to lipopolysaccharide markedly increased the FcγRI expression in naive Eos, which could be bound by Ag-specific IgG (sIgG) to form complexes on the surface of Eos; this made Eos at the sensitized status. Eos bore with the sIgG/FcγRI complexes could be activated upon exposure to sIgG in the culture; these Eos can be designated as Ag-specific Eos. Passive transfer of Ag-specific Eos resulted in profound AR response in mice upon sAg challenge. Depletion of FcγRI on Eos efficiently abolished AR response in mice. Conclusions AR Eos express high levels FcγRI, that can be bound by sIgG to make Eos sensitized. Re-exposure to specific Ags can activate the sensitized Eos.

Flagellin Alleviates Airway Allergic Response by Stabilizing Eosinophils through Modulating Oxidative Stress

“…Exposure to specific antigens can induce oxidative stress in Eos in the tissues with allergic lesions. This is supported by the previous reports in which the exposure to specific antigens can activate Eos by binding the specific IgG/FcγRI or/and FcγRIII on the surface of Eos [9, 20].…”

“…2a). The previous reports indicate that specific antigen/IgG complexes bind FcγRI or FcγRIII on the Eo surface to sensitize and activate Eos [9, 20]. Thus, Eos were sensitized by exposing to anti-OVA IgG in the culture overnight.…”

“…The published data indicate that the Eo activation results in oxidative stress [21], whether the oxidative species are increased inside Eos in response to exposing specific antigens remain to be elucidated. Prompted by the fact of exposing to specific antigens can activate sensitized Eos [9], we developed an asthma mouse model; the mice were challenged with nasal instillation containing the specific antigen, OVA, together with or without FGN in the course of sensitization. After the sacrifice, the single cells were isolated from the lung tissues and analyzed by FCS.…”

“…However, these stimulatory factors generally exist in the human body, why Eos are not activated under physiological conditions is incompletely understood. Specifically, the IgG Abs generally exist in the body and have chances to contact the FcγRs on the surface of Eos [9]; how Eos maintain the stabilization status in a healthy condition also remains to be investigated.…”

Deletion of Arno Reduces Eosinophilic Inflammation and Interleukin-5 Expression in a Murine Model of Rhinitis

“…1,7 Furthermore, there is often an accumulation of eosinophils in the nasal cavity which may further drive the disease pathophysiology. 8 ARF nucleotide-binding site opener (ARNO), also known as cytohesin-2, is a guanine nucleotide-exchange factor for ADPribosylation factor GTPases. 9 ARF nucleotide-binding site opener is a member of the cytohesin family, which are characterized by a heptad repeat coiled coil, Sec7, and pleckstrinhomology domains.…”