Granulocyte macrophage colony stimulating factor induces FcεRII/CD23 expression on normal human polymorphonuclear neutrophils

Abstract

Three major molecules have been recognized as IgE-binding structures on hematopoietic cells: the heterotrimeric high-affinity receptor for IgE (Fc epsilon RI), the low-affinity receptor for IgE (Fc epsilon RII/CD23) and the Mac-2/IgE-binding protein (epsilon BP). The latter has been shown to be expressed on polymorphonuclear neutrophils (PMN), where it regulates IgE-dependent activation. Experiments were undertaken to determine whether the IgE-binding capacity of PMN is mediated exclusively by this molecule. No detectable binding of human myeloma IgE to unstimulated PMN from normal volunteers could be evidenced. In contrast, PMN stimulated with granulocyte macrophage colony stimulating factor (GM-CSF) (500 U/ml) for 24 h displayed positive IgE binding. This binding was significantly inhibited in the presence of mAb directed against Mac-2/epsilon BP and also in the presence of anti-CD23 mAb, but not of anti-Fc epsilon RI mAb or isotype-matched controls. By flow cytometry, CD23 expression was detected on GM-CSF-primed PMN by several anti-CD23 mAb, including EBVCS-5, BB10 or Mab135, which recognize different epitopes. CD23 was also evidenced by immunocytochemistry in GM-CSF-primed PMN. By in situ hybridization, GM-CSF-treated PMN exhibited a hybridization signal for CD23 mRNA and the presence of the CD23b isoform-specific mRNA was detected by RT-PCR. These findings indicate that PMN can synthesize CD23 molecules under GM-CSF induction. This strong CD23 expression might be of physiopathological relevance in IgE-dependent activation during allergic processes.

Neutrophils as a Novel Source of Eosinophil Cationic Protein in IgE-Mediated Processes

“…The presence of the three forms of IgE-receptor/IgE-binding molecule (FcRI, FcRII/CD23, and BP/mac-2/galectin-3) has previously been reported in neutrophils (32)(33)(34)(35)(36). The next experiments were performed to identify the types of IgE receptor/IgEbinding molecule involved in IgE-dependent ECP release.…”

“…Several studies have reported evidence linking the presence of neutrophils with airway damage and dysfunction (29 -31). IgE can bind on neutrophils at the high-affinity receptor for IgE (FcRI) (32), the lowaffinity receptor for IgE (FcRII/CD23) (33,34), and galectin-3 (35,36). We have previously shown that specific Ags were able to activate functional responses by neutrophils from allergic patients sensitized to Ags of the same type as those which produce clinical allergic symptoms.…”

IgE Modulates Neutrophil Survival in Asthma: Role of Mitochondrial Pathway

“…To date, three types of IgE receptor have been identified in neutrophils: galactin 3 (Mac-2/BP) (17), the low-affinity receptor (FcRII/CD23) (18), and the high-affinity FcRI (11). FcRI binds IgE with a much higher affinity (Ͼ1000-fold) than FcRII (19) and in AA neutrophils IgE primarily binds FcRI (11).…”

Specific Allergens Enhance Elastase Release in Stimulated Neutrophils from Asthmatic Patients

“…Earlier studies have demonstrated the presence of the three forms of IgE receptor on human neutrophils [16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26]. We have previously shown that specific allergens were able to activate functional responses by neutrophils from allergic patients sensitized to allergens of the same type as those which produce clinical allergic symptoms [27].…”

“…Elastase is a proteolytic enzyme contained in the azurophilic granules of neutrophils, and has been reported to cause epithelial damage [10], vascular hyperpermeability [11], mucus hypersecretion [12], mucus gland metaplasia [13], reduction in mucociliary clearance [14], bronchoconstriction and airway hyperresponsiveness [15]. Previous studies have demonstrated the presence of the three forms of IgE receptor – the heterotrimeric high-affinity receptor for IgE (FcεRI) [16, 17, 18, 19], the low-affinity receptor for IgE (FcεRII/CD23) [20, 21, 22]and galectin-3 [23, 24, 25, 26]– on human neutrophils. We have previously shown that specific allergens were able to activate functional responses by neutrophils from allergic patients sensitized to allergens of the same type that produced clinical allergic symptoms [27].…”