کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2831730 | 1570741 | 2010 | 9 صفحه PDF | دانلود رایگان |
Heparanase is a heparan sulfate (HS) degrading endoglucuronidase that has been implicated in cell migration and inflammatory conditions. Here we used mice deficient of heparanase (Hpse−/−) to study the impact of heparanase on airway leukocytes. Normal numbers of macrophages and lymphocytes were present in bronchoalveolar lavage fluid of Hpse−/− mice, indicating that heparanase is not essential for proper homing of leukocytes to airways. While lymphocytes from Hpse−/− mice displayed normal morphology, Hpse−/− alveolar macrophages showed a striking, age-dependent appearance of granule-like structures in the cytoplasm. Transmission electron microscopy revealed that these structures corresponded to membrane-enclosed crystalline bodies that closely resembled the intracellular crystals known to be formed by the HS-binding protein Ym1, suggesting that heparanase deficiency is associated with intracellular Ym1 deposition. Indeed, applying immunocytochemistry, we found markedly higher levels of intracellular Ym1 protein in Hpse−/− versus WT alveolar macrophages, and there was a significant correlation between levels of Ym1 protein detected by immunoblotting and amounts of crystalline material in BAL cells. Biosynthetic radio-labeling of the macrophages revealed accumulation of non-degraded HS chains in Hpse−/− macrophages. Together, these findings implicate heparanase in normal processing of HS in macrophages, and indicate that heparanase regulates intracellular Ym1 accumulation and crystal formation in airways.
Journal: Molecular Immunology - Volume 47, Issues 7–8, April 2010, Pages 1467–1475