1. Plasminogen activator inhibitor-2 (PAI-2) in eosinophilic leukocytes.
- Author
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Swartz JM, Byström J, Dyer KD, Nitto T, Wynn TA, and Rosenberg HF
- Subjects
- Animals, Bone Marrow metabolism, Bone Marrow pathology, Eosinophils parasitology, Granuloma parasitology, Humans, Interleukin-5 genetics, Interleukin-5 physiology, Liver parasitology, Mice, Ovum parasitology, Eosinophils immunology, Plasminogen Activator Inhibitor 2 metabolism, Schistosoma mansoni pathogenicity, Urokinase-Type Plasminogen Activator metabolism
- Abstract
Plasminogen activator inhibitor-2 (PAI-2) as a potential eosinophil protein was inferred from our gene microarray study of mouse eosinophilopoiesis. Here, we detect 47 kDa intracellular and approximately 60 kDa secretory forms of PAI-2 in purified human eosinophil extracts. PAI-2 is present at variable concentrations in eosinophil lysates, ranging from 30 to 444 ng/10(6) cells, with a mean of 182 ng/10(6) cells from 10 normal donors, which is the highest per-cell concentration among all leukocyte subtypes evaluated. Enzymatic assay confirmed that eosinophil-derived PAI-2 is biologically active and inhibits activation of its preferred substrate, urokinase. Immunohistochemical and immunogold staining demonstrated PAI-2 localization in eosinophil-specific granules. Immunoreactive PAI-2 was detected in extracellular deposits in and around the eosinophil-enriched granuloma tissue encapsulating the parasitic egg in livers of wild-type mice infected with the helminthic parasite Schistosoma mansoni. Among the possibilities, we consider a role for eosinophil-derived PAI-2 in inflammation and remodeling associated with parasitic infection as well as allergic airways disease, respiratory virus infection, and host responses to tumors and metastasis in vivo.
- Published
- 2004
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