Eosinophil major basic protein: First identified natural heparanase-inhibiting protein

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:113

Article

Temkin, V ; Aingorn, H ; Puxeddu, I ; Goldshmidt, O ; Zcharia, E ; Gleich, GJ ; Vlodavsky, I ; Levi-Schaffer, F

关键词: heparanase;    eosinophils;    major basic protein;    inflammation;    angiogenesis;    fibrosis;    metastasis;    allergic peritonitis;   

DOI  :  10.1016/j.jaci.2003.11.038

来源: Elsevier

【 摘 要 】

Background: Heparanase and eosinophils are involved in several diseases, including inflammation, cancer, and angiogenesis. Objective: We sought to determine whether eosinophils produce active heparanase. Methods: Human peripheral blood eosinophils were isolated by immunoselection and tested for heparanase protein (immunocytochemistry. Western blot), mRNA (RT-PCR) and activity (Na-2 [S-35]O-4-labeled extracellular matrix degradation) before and after activation. Heparanase intracellular localization (confocal laser microscopy) and ability to bind to eosinophil major basic protein (MBP) were also evaluated (immunoprecipitation). A model of allergic peritonitis resulting in eosinophilia was induced in TNF knockout and wild-type mice for in vivo studies. Results: Eosinophils synthesized heparanase mRNA and contained heparanase in the active (50-kd) and latent (65-kd) forms. Heparanase partially co-localized with and was bound to NOR No heparanase enzymatic activity was detected in eosinophils resting or activated with various agonists, including GM-CSF/C5a. Eosinophil lysates and MBP inhibited recombinant heparanase activity in a concentration-dependent manner (100%, 2 x 10(-7) mol/L). Eosinophil peroxidase and eosinophil cationic protein, but not myelin basic protein or compound 48/ 80, partially inhibited heparanase activity. Poly-(L)-arginine at very high concentrations caused an almost complete inhibition. In allergic peritonitis, heparanase activity in the peritoneal fluid inversely correlated with eosinophil number. Conclusions: MBP is the first identified natural heparanase inhibiting protein. Its presence in the eosinophil granules might indicate a protective function of these cells in diseases associated with inflammation and cancer progression.

【 授权许可】

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