Eosinophils and IgE receptors: a continuing controversy.

phils produce cytokines, such as interleukin-4 (IL-4) and D IL-5, which are potentially important in the recruitment of URING THE PAST 2 decades, considerable new information has been obtained about the functions of the eosinophils, thus causing chronic allergic inflammation. eosinophil and its roles in human disease. Presently, the Second, IgE bound to receptors on antigen-presenting cells, eosinophil is recognized as a proinflammatory granulocyte such as CD23 on B cells and to high-affinity IgE receptors implicated in protection against parasitic infections and be(FceRI) on Langerhans’ cells and monocytes, can enhance lieved to play a major role in allergic diseases, such as bronantigen internalization and presentation to T cells, resulting chial asthma, allergic rhinitis, and atopic dermatitis. The in continuous activation of the immune system. Finally, eosinophil is an important source of cytotoxic cationic proIgE may mediate killing of the invading helminth and host teins, such as major basic protein (MBP), eosinophil peroxicell damage by acting as a ligand for antibody-dependent dase, and eosinophil cationic protein. These proteins are pocell-mediated cytotoxicity (ADCC) by macrophages and tentially two-edged swords; on the one hand, they protect other immune cells. In fact, immunoepidemiological studthe host against overwhelming helminth infections, but on ies showed a significant correlation between the production the other hand, they damage the host’s tissues. Eosinophils of antischistosome IgE antibodies and the acquisition of imalso induce inflammation by releasing lipid mediators, oxymunity against reinfection to S haematobium. In allergic gen metabolites, and cytokines. Numerous studies have diseases such as bronchial asthma, there is a close correlation shown the association of eosinophils and various human between serum IgE levels and the prevalence and severity parasitic and allergic diseases. For example, at present, the of the diseases. Thus, there is now converging evidence to most common worldwide cause of eosinophilia is probably support roles for IgE in resistance to helminthic infections infection with helminths, and high eosinophil counts correand in the pathophysiology of allergic diseases in humans. late with lack of reinfection after treatment of Schistosoma Therefore, it is reasonable to speculate that IgE is involved haematobium infections. Analyses of patients infected with in the activation of eosinophils in these diseases. Onchocerca volvulus have shown striking deposition of the Early studies on the killing of schistosomula in vitro by eosinophil granule MBP around degenerating microfilaria. human eosinophils used cells purified from normal or In allergic asthma, eosinophilic and lymphocytic infiltration slightly eosinophilic individuals, together with heat-inactiin the epithelium and lamina propria of the airways are convated sera from individuals with schistosome infection. The sistently found even in mild and stable asthma. Indeed, results of these studies suggested that killing requires IgG correlations have been observed between the numbers of and is independent of complement. IgG1 and IgG3 subinfiltrating eosinophils and asthma disease severity. Pulmoclasses were effective in mediating ADCC by human eosinonary segmental allergen challenge in allergic individuals phils, whereas IgM, IgG2, and IgG4 were not only inactive, causes eosinophil recruitment into the airways; this is associbut blocked the effects of the active subclasses. A quite ated with the release of eosinophil granule proteins and the separate phenomenon was observed with low density, soincrease in vascular permeability. Despite the strong assocalled hypodense eosinophils that can be isolated from indiciations among eosinophils, their cytotoxic granule proteins, viduals with very high eosinophil counts. Receptors for IgE and human diseases, the mechanism(s) responsible for eosinwere identified on both rat and human hypodense eosinoophil activation in vivo is largely unknown. phils, and hypodense human eosinophils were shown to Helminth infections and allergic diseases are characteristikill schistosomula in the presence of IgE. Subsequently, cally associated not only with peripheral blood and tissue this human eosinophil IgE receptor was shown to be similar, eosinophilia, but also with high levels of both total and antigen-specific IgE antibodies. IgE antibodies may be involved in disease in three ways. First, the central feature in From the Departments of Immunology and Medicine, Mayo Clinic anaphylactic and immediate hypersensitivity reactions is and Mayo Foundation, Rochester, MN. IgE-dependent activation of mast cells and basophils leading Address reprint requests to Hirohito Kita, MD, Department of to the release of histamine and other inflammatory mediators, Immunology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. such as prostaglandins and leukotrienes. Furthermore, upon q 1997 by The American Society of Hematology. 0006-4971/97/8910-0042$3.00/0 activation through IgE receptors, human mast cells and baso-