title: Mice deficient in heparanase exhibit impaired dendritic cell migration and reduced airway inflammation.
abstract: Heparanase is a β-d-endoglucuronidase that cleaves heparan sulphate, a key component of the ECM and basement membrane. The remodelling of the ECM by heparanase has been proposed to regulate both normal physiological and pathological processes, including wound healing, inflammation, tumour angiogenesis and cell migration. Heparanase is also known to exhibit non-enzymatic functions by regulating cell adhesion, cell signalling and differentiation. In this study, constitutive heparanase-deficient (Hpse(-/-) ) mice were generated on a C57BL/6 background using the Cre/loxP recombination system, with a complete lack of heparanase mRNA, protein and activity. Although heparanase has been implicated in embryogenesis and development, Hpse(-/-) mice are anatomically normal and fertile. Interestingly, consistent with the suggested function of heparanase in cell migration, the trafficking of dendritic cells from the skin to the draining lymph nodes was markedly reduced in Hpse(-/-) mice. Furthermore, the ability of Hpse(-/-) mice to generate an allergic inflammatory response in the airways, a process that requires dendritic cell migration, was also impaired. These findings establish an important role for heparanase in immunity and identify the enzyme as a potential target for regulation of an immune response.
authors.affiliation: Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
authors.forename: Ivan K H
authors.initials: IK
authors.lastname: Poon
authors.forename: Katharine J
authors.initials: KJ
authors.lastname: Goodall
authors.forename: Simon
authors.initials: S
authors.lastname: Phipps
authors.forename: Jenny D Y
authors.initials: JD
authors.lastname: Chow
authors.forename: Eloisa B
authors.initials: EB
authors.lastname: Pagler
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Andrews
authors.forename: Carly L
authors.initials: CL
authors.lastname: Conlan
authors.forename: Gemma F
authors.initials: GF
authors.lastname: Ryan
authors.forename: Julie A
authors.initials: JA
authors.lastname: White
authors.forename: Michael K L
authors.initials: MK
authors.lastname: Wong
authors.forename: Catherine
authors.initials: C
authors.lastname: Horan
authors.forename: Klaus I
authors.initials: KI
authors.lastname: Matthaei
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hulett
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D005966:Glucuronidase / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D011014:Pneumonia / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology / Q000378:metabolism; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D000099175:Heparanase
keywords: Allergy; DC; Heparanase; Inflammation; Migration