Published online before print July 26, 2004

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(Journal of Leukocyte Biology. 2004;76:812-819.)
© 2004 by Society for Leukocyte Biology

Plasminogen activator inhibitor-2 (PAI-2) in eosinophilic leukocytes

Jonathan M. Swartz^*, Jonas Byström^*, Kimberly D. Dyer^*, Takeaki Nitto^*, Thomas A. Wynn and Helene F. Rosenberg^*,1

^* Laboratories of Allergic Diseases and
Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

¹Correspondence: Building 10, Room 11N104, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892. E-mail: hrosenberg{at}niaid.nih.gov

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 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/10⁶ cells, with a mean of 182 ng/10⁶ 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.

Key Words: eosinophils • proteases • protease inhibitor • secretory proteins • serpin

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