| First Author | Waern I | Year | 2010 |
| Journal | Mol Immunol | Volume | 47 |
| Issue | 7-8 | Pages | 1467-75 |
| PubMed ID | 20226534 | Mgi Jnum | J:160638 |
| Mgi Id | MGI:4454749 | Doi | 10.1016/j.molimm.2010.02.004 |
| Citation | Waern I, et al. (2010) Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase. Mol Immunol 47(7-8):1467-75 |
| abstractText | 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. |
