Control of Eosinophil Toxicity in the Lung

Abstract

The inappropriate accumulation of eosinophils and the subsequent release of their potent pro-inflammatory mediator arsenal are thought to be important contributors to the pathogenesis of asthma and other allergic diseases. It is also becoming apparent that eosinophils may play a role in the orchestration of immune responses in the asthmatic lung. There is therefore much interest in the development of strategies to limit or prevent eosinophil-induced toxicity. The mechanisms by which eosinophils accumulate in the peribronchial tissues of the lung are complex and include enhanced differentiation and release from the bone marrow, selective adhesion and transendothelial migration, directed movement in response to specific chemotactic mediators and finally prolonged survival as a consequence of delayed apoptosis. Thus it can be appreciated that there are many points at which the toxicity of eosinophils can be limited or even prevented. Important areas for potential advances in glucocorticoid (GC) development include efforts to dissociate their anti-inflammatory effects from unwanted side effects. Other areas include the development of humanized monoclonal antibodies against IL-4, IL-13 and IL-5 together with the inhibition of adhesion pathways and/or chemokines responsible for eosinophil accumulation in the asthmatic lung. Several avenues of research are currently underway in an attempt to define mechanisms by which pro-inflammatory cells such as eosinophils can be safely removed from the asthmatic lung through apoptosis induction and their subsequent ingestion by phagocytes. This review will discuss both the potential and shortcomings of these diverse approaches to limit eosinophil toxicity in the asthmatic lung.

Effective antigen presentation to helper T cells by human eosinophils

“…(1,2) Asthma is now recognised as a heterogeneous condition with a number of phenotypes, some of which are stratified according to cellular infiltrates such as neutrophilic or eosinophilic asthma. (3) Eosinophilic asthma is characterized by increased blood or sputum eosinophils, (4) the numbers of which correlate with disease severity. (5) Infiltrating tissue eosinophils release their potent pro-inflammatory arsenal that includes such diverse elements as granule-derived basic proteins, lipid mediators, cytokines and chemokines.…”

Regulation of Arachidonate Remodeling Enzymes Impacts Eosinophil Survival during Allergic Asthma

“…If allowed to accumulate in tissues, eosinophils can release a wide variety of proinflammatory mediators including cytotoxic granule proteins, lipid mediators, and cytokines, thereby exacerbating inflammatory diseases such as allergic asthma (1). In vivo, normal induction of eosinophil death by apoptosis facilitates their clearance by macrophages and other phagocytic cells (2).…”

Apoptosis: A Therapeutic Strategy in Eosinophilia

“…Amongst the best characterized members of death receptors, CD95 (Fas) is exposed to encourage apoptosis in lymphocytes and mimicked by novel anti asthma drugs [11,66]. Apoptosis in eosinophils is followed by CD95 (Fas) and CD95L (FasL) ligand system that forms complex called DISC [67] and the activated T cells express these death receptors [68].…”