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Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase

Waern, Ida and Pejler, Gunnar and Wernersson, Sara and Jia, Juan and Li, Jin-ping and Vlodavsky, Israel and Zcharia, Eyal (2010). Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase. Molecular Immunology. 47:7-8, 1467-1475
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Official URL: http://dx.doi.org/10.1016/j.molimm.2010.02.004

Abstract

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 crystalsknown 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.

Authors/Creators:Waern, Ida and Pejler, Gunnar and Wernersson, Sara and Jia, Juan and Li, Jin-ping and Vlodavsky, Israel and Zcharia, Eyal
Title:Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase
Series/Journal:Molecular Immunology (0161-5890)
Year of publishing :2010
Volume:47
Number:7-8
Page range:1467-1475
Number of Pages:8
Publisher:Elsevier
ISSN:0161-5890
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Accepted version
Full Text Status:Public
Agris subject categories.:L Animal production > L50 Animal physiology and biochemistry
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 402 Animal and Dairy Science
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science
Keywords:Heparanase knockout mice , Heparan sulfate, Chitinase-like protein, Alveolar macrophages, Airway inflammation
URN:NBN:urn:nbn:se:slu:epsilon-e-1652
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-1652
Additional ID:
Type of IDID
Web of Science (WoS)000277862300010
DOI10.1016/j.molimm.2010.02.004
ID Code:10837
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
Deposited By: SLUpub Connector
Deposited On:08 Oct 2013 13:40
Metadata Last Modified:31 Mar 2015 21:17

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