Plasminogen activator inhibitor-2 (PAI-2) in eosinophilic leukocytes.
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.
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Jonathan M
JM
Swartz
Jonas
J
Byström
Kimberly D
KD
Dyer
Takeaki
T
Nitto
Thomas A
TA
Wynn
Helene F
HF
Rosenberg
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D004804:Eosinophils / Q000276:immunology* / Q000469:parasitology; D006099:Granuloma / Q000469:parasitology; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000469:parasitology; D051379:Mice; D010063:Ovum / Q000469:parasitology; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000472:pathogenicity*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D015848:Interleukin-5; D017396:Plasminogen Activator Inhibitor 2; D014568:Urokinase-Type Plasminogen Activator