title: Efferocytosis is impaired in Gaucher macrophages.
abstract: Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylceramide-laden macrophages resulting from impaired digestion of aged erythrocytes or apoptotic leukocytes. Studies of macrophages from patients with type 1 Gaucher disease with genotypes N370S/N370S, N370S/L444P or N370S/c.84dupG revealed that Gaucher macrophages have impaired efferocytosis resulting from reduced levels of p67phoxand Rab7. The decreased Rab7 expression leads to impaired fusion of phagosomes with lysosomes. Moreover, there is defective translocation of p67phoxto phagosomes, resulting in reduced intracellular production of reactive oxygen species. These factors contribute to defective deposition and clearance of apoptotic cells in phagolysosomes, which may have an impact on the inflammatory response and contribute to the organomegaly and inflammation seen in patients with Gaucher disease.
authors.affiliation: Section of Molecular Neurogenetics, Medical Genetics Branch, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Elma
authors.initials: E
authors.lastname: Aflaki
authors.affiliation: Section of Molecular Neurogenetics, Medical Genetics Branch, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Borger
authors.affiliation: Section of Molecular Neurogenetics, Medical Genetics Branch, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Grey
authors.affiliation: Flow Cytometry Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Kirby
authors.affiliation: Flow Cytometry Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Stacie
authors.initials: S
authors.lastname: Anderson
authors.affiliation: Section of Molecular Neurogenetics, Medical Genetics Branch, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Grisel
authors.initials: G
authors.lastname: Lopez
authors.affiliation: Section of Molecular Neurogenetics, Medical Genetics Branch, National Institutes of Health, Bethesda, MD, USA sidranse@mail.nih.gov.
authors.forename: Ellen
authors.initials: E
authors.lastname: Sidransky
mesh_terms: D015415:Biomarkers; D057899:Cytophagocytosis / Q000235:genetics / Q000276:immunology; D005776:Gaucher Disease / Q000235:genetics* / Q000276:immunology*; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D009154:Mutation; D010587:Phagocytosis / Q000235:genetics* / Q000276:immunology*; D010588:Phagosomes / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000235:genetics / Q000276:immunology
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D005962:Glucosylceramidase