New Aspects of Degranulation and Fates of Airway Mucosal Eosinophils
Authors: JONAS S. ERJEFÄLT, CARL G. A. PERSSON
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Eosinophils are bone marrow-derived granulocytes with a richness of surface receptors for immunologic ligands (1–4). Eosinophils characteristically harbor specific granules which, besides some 20 known chemokines, cytokines, and growth factors, contain large amounts of the tissue-toxic cationic proteins major basic protein, eosinophil cationic protein (ECP), eosinophil peroxidase, and eosinophil-derived neurotoxin (5, 6). Given these properties, eosinophils may have many roles in tissue, ranging from immunoregulation (7) to tissue remodelling and repair (8–10) and the killing of foreign organisms (1–4). Eosinophils abounding and degranulating in airway mucosal and pulmonary tissues are also believed to have pathogenic roles in asthma, nasal polyposis, allergic rhinitis, and eosinophilic pneumonia (11, 12). Increased levels of granule proteins such as ECP in body fluids (13), and specific ultrastructural features of tissue eosinophils (14, 15) (Table 1), reflect eosinophil degranulation activity. At the light-microscopic level, immunohistochemical staining with the monoclonal antibody EG2 (23) has been widely used to identify degranulating tissue eosinophils. Similarly, terminal deoxynucleotidyl transferase-uridine nucleotide endlabeling (TUNEL) technique has recently been used to examine the occurrence of apoptotic eosinophils in the airways (24, 25). However, these commonly used markers of eosinophil activation and death, respectively, may not always be specific. For example, EG2 staining may merely indicate eosinophils in general (26), and the capacity of TUNEL techniques to clearly distinguish between apoptosis and necrosis (cytolysis) is currently debated (27–29). Indeed, the TUNEL technique must be combined with analysis of cell morphology in the assessment of apoptosis. In the absence of acceptable molecular markers, and to complement the determination of eosinophil proteins, morphologic changes will have to be assessed to identify and quantify modes of degranulation and fates of airway mucosal eosinophils (15) (Table 1). Many eosinophils that dwell in the airway mucosa may enter the airway lumen (Figure 1). Some eosinophils may move to the regional lymph nodes (30–32). Others remain in the airway mucosa until they die. As demonstrated in in vitro test systems, death of eosinophils may occur silently through apoptosis (33, 34). On the other hand, observations of diseased airway mucosae indicate that these cells may instead die through the mechanism of eosinophil cytolysis, which simultanously acts as an ultimate mode of degranulation (16). Airway tissue eosinophils may thus have several different fates in vivo (Figure 1), each with its own potential significance. The present article deals with clearance pathways for airway mucosal eosinophils, such as “luminal entry,” eosinophil apoptosis, and eosinophil cytolysis. We further discuss eosinophil cytolysis as a major mode of degranulation of eosinophils in airway diseases, in addition to piecemeal degranulation (PMD; Table 1, Figure 2). As in other areas of airway research (35, 36), in vitro research standards relating to eosinophil events may partly diverge from what actually occurs in bloodperfused airway tissue. Hence, the present emphasis is on in vivo observations.