title: Haematopoietic development and immunological function in the absence of cathepsin D.
abstract: BACKGROUND
  Cathepsin D is a well-characterized aspartic protease expressed ubiquitously in lysosomes. Cathepsin D deficiency is associated with a spectrum of pathologies leading ultimately to death. Cathepsin D is expressed at high levels in many cells of the immune system, but its role in immune function is not well understood. This study examines the reconstitution and function of the immune system in the absence of cathepsin D, using bone marrow radiation chimaeras in which all haematopoietic cells are derived from cathepsin D deficient mice.
  
  
  RESULTS
  Cathepsin D deficient bone marrow cells fully reconstitute the major cellular components of both the adaptive and innate immune systems. Spleen cells from cathepsin D deficient chimaeric mice contained an increased number of autofluorescent granules characteristic of lipofuscin positive lysosomal storage diseases. Biochemical and ultrastructural changes in cathepsin D deficient spleen are consistent with increased autolysosomal activity. Chimaeric mice were immunised with either soluble (dinitrophenylated bovine gamma globulin) or particulate (sheep red blood cells) antigens. Both antigens induced equivalent immune responses in wild type or cathepsin D deficient chimaeras.
  
  
  CONCLUSIONS
  All the parameters of haematopoietic reconstitution and adaptive immunity which were measured in this study were found to be normal in the absence of cathepsin D, even though cathepsin D deficiency leads to dysregulation of lysosomal function.
authors: Division of Infection and Immunity, UCL, London, UK. r.tulone@ucl.ac.uk
authors: Calogero
authors: C
authors: Tulone
authors: Yasuo
authors: Y
authors: Uchiyama
authors: Marco
authors: M
authors: Novelli
authors: Nicholas
authors: N
authors: Grosvenor
authors: Paul
authors: P
authors: Saftig
authors: Benjamin M
authors: BM
authors: Chain
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D002402:Cathepsin D / Q000172:deficiency* / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006410:Hematopoiesis; D007113:Immunity, Innate; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D002402:Cathepsin D