No abstract

SummaryIt has been suggested that neutrophils may be involved in the late-phase reaction of immunoglobulin E (IgE)-dependent hypersensitivity states. However, the identity of neutrophil-associated molecules inducing the release of mediators remains undear. In this report, we demonstrate that human neutrophils from normal donors or from patients with inflammatory disorders could bind myeloma IgE proteins, especially after desialylation. Northern blot, immunoprecipitation, and flow cytometry analyses revealed that neutrophils did not express FceRII/CD23, but rather Mac-2/e binding protein (BP), belonging to the S-type lectin family. Similarly to IgA used as positive control, myeloma IgE proteins, as well as polyclonal IgE antibodies with or without antibody specificity, were both capable of inducing a neutrophil respiratory burst. Anti-Mac-2 but not anti-CD23 mAb strongly decreased the IgE-dependent activation of neutrophils, induced either by the specific antigen or by anti-IgE antibodies. These findings open new perspectives on the functional role of neutrophils in IgE-associated diseases including allergic states or parasitic infections.I nflammatory reactions generally involve a vast array of mediators and a variety of effector cells such as mast cells, macrophages, eosinophils, platelets, and neutropb.ils. Among them, neutrophils have been rather neglected in studies concerning allergic diseases, although an increase in neutrophil numbers and activity was found to be correlated to airway hyperresponsiveness in asthmatic patients (1). These findings have suggested that neutrophils might play a role in allergic diseases characterized by a marked elevation of serum IgE, such as asthma, especially during the late-phase reaction. However, neutrophils represent the only blood cell population that does not seem to express conventional Fc receptors for IgE, neither FceRI, like basophils or mast cells (2), nor FceRII, like macrophages, eosinophils, or platelets (3). Besides these IgE Fc receptors, a new family of IgE-binding molecules has been recently described. They belong to S-type lectins with the ability to bind IgE through carbohydrate recognition domain (4). Members of the family include Mac-2/eBP, which are endogenous soluble lectins and can be expressed by various cell types (5, 6). One feature of eBP molecules is their restricted recognition by specific glycoforms of IgE. It is interesting that the majority of myeloma IgE proteins and polydonal IgE from some patients are able to bind to eBP only after desialylation (5, 7). In this respect, it has to be mentioned that the few IgE binding assays previously reported on human neutrophils (8, 9) have been performed with myeloma IgE proteins, and therefore did not allow us to investigate the existence of functional interactions between neutrophils and IgE antibodies from patients. The wide cell distribution of Mac-2/eBP molecules and their recent demonstration in eosinophils from hypereosinophilic patients (10) led us to investigate their possible existence in hum...

The existence of a functional receptor for secretory component (SC) on the eosinophil membrane might explain the preferential degranulation induced by secretory IgA (sIgA) when compared to serum IgA. Indeed, flow cytometry analysis revealed that purified human SC could bind to a subpopulation (4-59%) of blood eosinophils purified from 19 patients with eosinophilia. Binding of radiolabeled human SC could be competitively inhibited using unlabeled SC or secretory IgA but not with serum IgA or IgG. Immunoprecipitation and immunosorbent chromatography using human SC revealed the presence of a major component at 15 kDa in eosinophil extracts as well as in culture supernatants but not in neutrophils. The 15-kDa protein eluted from the human SC immunosorbent was able to bind to SC or to sIgA but not to serum IgA. Eosinophils preincubated with human SC or sIgA released eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) after addition of anti-SC or anti-IgA monoclonal antibody as respective cross-linking reagents. These results indicated that binding of free or complexed SC to human eosinophils could induce eosinophil degranulation. Furthermore, the dose-dependent inhibition by SC of mediator release induced by sIgA but not by serum IgA, suggested that the receptor for SC could be involved in the preferential degranulation mediated by sIgA. These results indicate a novel pathway of eosinophil activation and its potential involvement in mucosal immunity, particularly in inflammatory diseases associated with infiltration of eosinophils and the enhanced production of sIgA.