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 p67phox and Rab7. The decreased Rab7 expression leads to impaired fusion of phagosomes with lysosomes. Moreover, there is defective translocation of p67phox to phagosomes, resulting in reduced intracellular reactive oxygen species production. These factors contribute to defective deposition and clearance of apoptotic cells in phagolysosomes, which may impact the inflammatory response and contribute to the organomegaly and inflammation seen in patients with Gaucher disease.
- Received August 25, 2016.
- Accepted December 16, 2016.
- Copyright © 2016, Ferrata Storti Foundation