Eosinophil-derived neurotoxin EDN

Bronchial Asthma. Figure 2 Mechanisms of bronchial hyperresponsiveness. Toxic products from eosinophils [cationic peptides, reactive oxygen species (ROS)] cause epithelial injury. Nerve endings become easily accessible to mediators from mast cells, eosinophils [eosinophil-derived neurotoxin (EDN)], and neutrophils, and to airborne toxicants such as S02. Activation of nerve endings stimulates effector cells like mucosal glands and airway smooth muscle either directly or by cholinergic reflexes. 

Eosinophil-derived neurotoxin (EDN) is another protein that is found in the granule matrix of eosinophils and it exhibits significant sequence homology with ECP (Barker et al., 1989). As implied by its name, EDN has a powerfiil neurotoxic action that can dam e myelinated neurones in experimental animals (Durack et al., 1981). However, unlike ECP or MBP there is no significant... 

Some members of the human RNase A superfamily of proteins are known to have host defense activities (reviewed in ref. 9). These include, for example, two of the eosinophil cytotoxic granular proteins, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN) (10). Angiogenin, a protein 65 % homologous to pancreatic RNase (11,12) that was originally isolated on the basis of its angiogenic activity (13), is a potent inhibitor of protein synthesis in the rabbit reticulocyte lysate (14) and when injected into Xenopus oocytes (15). We have therefore sought to fuse RNases to MAbs to evaluate their usefulness as immunotoxins (16,17). 

Upon activation, eosinophils release cytotoxic enzymes, e.g., eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase (EPO). Extravascular ECP (8) and MBP (9) deposits have been observed, and high levels of eosinophil cytotoxic enzymes are found in CSS patient s sera, urine, and bronchoalveolar fluids (9-11). In addition, the results of a recent study suggested that EPO released by activated eosinophils could cause oxidative tissue damage (12). Taken together, these elements incriminate eosinophil cytotoxicity in CSS development. 

ED35 Eflective dose producing 35% maximum response EDso Effective dose producing 50% maximum response EDF Eosinophil differentiation 6ctor EDL Extensor digitorum longus EDN Eosinophil-derived neurotoxin EDRF Endothelium-derived relaxing factor... 

DDBJ—see EMBL DLS—dynamic light scattering DM—donkey s milk DNA—deoxyribonucleic acid DNCB—2,4-dinitrochlorobenzene DSC—differential scanning calorimetry DTH—delayed cellular hypersensitivity DXMS—deuterium exchange mass spectrometry EAACI—European Academy of Allergology and Clinical Immunology EAR—early anaphylactic phase ECFA—eosinophil chemotactic factors of anaphylaxis ECP—eosinophil cationic protein EDN—eosinophil-derived neurotoxin eHF—extensively hydrolyzed formula ELISA—enzyme-linked immunosorbent assay... 

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