uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Show others and affiliations
2010 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 47, no 7-8, 1467-1475 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2010. Vol. 47, no 7-8, 1467-1475 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-135454DOI: 10.1016/j.molimm.2010.02.004ISI: 000277862300010PubMedID: 20226534OAI: oai:DiVA.org:uu-135454DiVA: diva2:375043
Available from: 2010-12-07 Created: 2010-12-07 Last updated: 2011-06-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Li, Jin-Ping
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
Molecular Immunology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 244 hits
ReferencesLink to record
Permanent link

Direct link