The role of the eosinophil in the pathogenesis of asthma

Eosinophils were first clearly identified by Ehrlich in 1879 (56) and the association of increased numbers of blood eosinophils with asthma was soon recognized (33). It is now well established that large numbers of eosinophils, together with mononuclear cells, are frequently present in and around the bronchi of patients who have died from asthma (31), CharcotLeyden-crystals (CLC) are another well-known eosinophil associated feature of the asthma process, which has now been identified as membrane-derived lysophospholipase (118), There has been a continuing debate regarding the role of eosinophils in asthma. In short, do they ameliorate the inflammatory process or promote it (117)? On the one hand eosinophil-derived products biodegrade mediators such as the peptide leukotrienes, which comprise the slow-reacting substance of anaphylaxis (leukotriene (LT) C4, D ,̂ E^). This is achieved through both oxidation to their respective sulphoxides and by conversion to the 6-trans diastereoisomers of leukotriene (LT) B4 by granule-derived eosinophil peroxidase (54, 119). The original observation that eosinophil-derived arylsulphatase could deactivate SRS-A was probably due to biodegradation of LTC4 to LTE4 by contaminating dipeptidases (73, 114). Similarly eosinophils also contain histaminase located in the granule compartment which oxidizes histamine to its catabolite imidazole acetic acid (121). However, in recent years increased understanding of the biology of the eosinophil, particularly with regard to their granule and membrane-derived products, has emphasized a pro-inflammatory rather than homeostatic role for this cell type. Many investigators now believe that eosinophils are a major effector of tissue damage in asthma (63), Several recent clinical studies, particularly those involving bronchoalveolar lavage, have provided more direct evidence to support this concept. The purpose of this review is to examine some recent findings on the biology of the eosinophil which might be relevant to the role of this cell in asthma and to evaluate various clinical studies which have identified an association between eosinophils, the late-phase response to antigen challenge, non-specific bronchial hyperreactivity and day-to-day asthma. All the work referred to has been performed on human eosinophils unless otherwise stated.