In this study, we characterize the sequences required for the cleavage of prohormones in Xenopus oocytes. We demonstrate that the yeast a-factor and the Aplysia egglaying hormone (ELH) precursors are not cleaved in oocytes following simple pairs of basic residues, such as Lys-Arg, but that the ELH precursor is cleaved following the consensus sequence Arg-Xaa-(Lys/Arg)-Arg. This motif is conserved among precursors that are cleaved in virtually all mammalian cell types. Mutations that generate this sequence in the a-factor prohormone also result in efficient processing within oocytes. Cleavage at this consensus sequence may be due to the action of the Xenopus homologues of mammalian furin.

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-1␣ (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.Tropical pulmonary eosinophilia (TPE), an unusual manifestation of human lymphatic filarial infection, is characterized by an eosinophilic pulmonary inflammatory infiltrate and marked elevations of immunoglobulin E (IgE) and circulating eosinophils in the serum, all felt to be mediated by immunologic hyperreactivity to filarial parasites or their antigens. Although 129 million people worldwide are infected with lymphatic filariasis, Ͻ0.01% develop TPE (20). It is unclear what factors predispose patients to the rare, localized, and profound immune dysregulation associated with TPE.