Plasminogen activator inhibitor-2 (PAI-2) in eosinophilic leukocytes
Jonathan M Swartz1, Jonas Byström, Kimberly D Dyer
1Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
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.
Insights
Plasminogen activator inhibitor-2 (PAI-2) is a biologically active protein found in human eosinophils at the highest concentration among leukocytes. Eosinophil-derived PAI-2 plays a role in inflammation and tissue remodeling during parasitic infections.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Plasminogen activator inhibitor-2 (PAI-2) was initially identified as a potential eosinophil protein through gene microarray studies.
- Eosinophils are key immune cells involved in inflammatory responses, particularly in parasitic infections and allergic diseases.
Purpose of the Study:
- To investigate the presence, characteristics, and localization of PAI-2 in human eosinophils.
- To determine the biological activity and potential roles of eosinophil-derived PAI-2 in inflammatory conditions.
Main Methods:
- Purification of human eosinophils and extraction of intracellular and secretory proteins.
- Enzymatic assays to assess PAI-2 activity against urokinase.
- Immunohistochemical and immunogold staining to localize PAI-2 within eosinophils and tissue.
Main Results:
- Detection of 47 kDa intracellular and ~60 kDa secretory forms of PAI-2 in human eosinophils.
- Eosinophils contain high concentrations of PAI-2 (mean 182 ng/10^6 cells), exceeding other leukocyte subtypes.
- Eosinophil-derived PAI-2 is biologically active, inhibiting urokinase, and localized in eosinophil-specific granules.
- Extracellular PAI-2 deposits were observed in granuloma tissue surrounding parasitic eggs in infected mice.
Conclusions:
- Human eosinophils are a significant source of biologically active PAI-2.
- Eosinophil-derived PAI-2 may contribute to inflammation and tissue remodeling in parasitic infections, allergic diseases, and other conditions.
More Related Videos
10:59Conditional Knockdown of Gene Expression in Cancer Cell Lines to Study the Recruitment of Monocytes/Macrophages to the Tumor Microenvironment
Published on: November 23, 2017
03:23Three-Dimensional Cell Culture Models to Investigate the Epithelial Barrier in Eosinophilic Esophagitis
Published on: May 10, 2024
Related Concept Videos
01:42Phosphoinositides and PIPs
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:09Cytoskeletal Linker Proteins - Plakins
01:26Acute Inflammation II: Cellular Phase