Localized eosinophil degranulation mediates disease in tropical pulmonary eosinophilia.
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.
O'Bryan
Laura
L
National Institutes of Health, Bethesda, Maryland, USA.
Pinkston
Paula
P
Kumaraswami
V
V
Vijayan
V
V
Yenokida
Gordon
G
Rosenberg
Helene F
HF
Crystal
Ronald
R
Ottesen
Eric A
EA
Nutman
Thomas B
TB
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
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases