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.
Swartz
Jonathan M
JM
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Byström
Jonas
J
Dyer
Kimberly D
KD
Nitto
Takeaki
T
Wynn
Thomas A
TA
Rosenberg
Helene F
HF
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