title: Localized eosinophil degranulation mediates disease in tropical pulmonary eosinophilia.
abstract: To explore the mechanisms underlying the eosinophil-mediated inflammation of tropical pulmonary eosinophilia (TPE), bronchoalveolar lavage (BAL) fluid, serum, and supernatants from pulmonary and blood leukocytes (WBC) from patients with acute TPE (n = 6) were compared with those obtained from healthy uninfected individuals (n = 4) and from patients with asthma (n = 4) or elephantiasis (n = 5). Although there were no significant differences in the levels of interleukin-4 (IL-4), IL-5, IL-13, eotaxin, granulocyte-macrophage colony-stimulating factor, RANTES, or eosinophil cationic protein, there was a marked increase in eosinophil-derived neurotoxin (EDN) both systemically and in the lungs of individuals with TPE compared to each of the control groups (P < 0.02). Moreover, there was a compartmentalization of this response, with EDN levels being higher in the BAL fluid than in the serum (P < 0.02). Supernatants from WBC from either whole blood or BAL cells were examined for chemokines, cytokines, eosinophil degranulation products, and arachidonic acid metabolites. Of the many mediators examined-particularly those associated with eosinophil trafficking-only EDN (in BAL fluid and WBC) and MIP-1alpha (in WBC) levels were higher for TPE patients than for the non-TPE control groups (P < 0.02). These data suggest it is the eosinophilic granular protein EDN, an RNase capable of damaging the lung epithelium, that plays the most important role in the pathogenesis of TPE.
authors.affiliation: National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: O'Bryan
authors.forename: Paula
authors.initials: P
authors.lastname: Pinkston
authors.forename: V
authors.initials: V
authors.lastname: Kumaraswami
authors.forename: V
authors.initials: V
authors.lastname: Vijayan
authors.forename: Gordon
authors.initials: G
authors.lastname: Yenokida
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
authors.forename: Ronald
authors.initials: R
authors.lastname: Crystal
authors.forename: Eric A
authors.initials: EA
authors.lastname: Ottesen
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000293:Adolescent; D000328:Adult; D001798:Blood Proteins / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015550:Cell Degranulation; D047091:Eosinophil Granule Proteins; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D011657:Pulmonary Eosinophilia / Q000209:etiology*; D012260:Ribonucleases / Q000032:analysis / Q000097:blood
chemical_list: D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases