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Impaired migration capacity in monocytes derived from patients with Gaucher disease.

Abstract

Gaucher disease (GD) is characterized by glucocerebroside (GC) accumulation due to defective activity of the glucocerebrosidase (GlcCerase) enzyme. Monocytes and macrophages exhibit the highest GlcCerase activity and are most prominently affected by GC engorgement. As GD patients tend to exert various immune system-related changes, this study was designed to investigate potential effects of monocyte dysfunction on these alterations. Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) of untreated GD patients and healthy volunteers. Monocyte migration capacity towards SDF1alpha was assessed. The GD patients exhibited reduced numbers of monocytes and decreased capability of SDF1alpha-dependent monocyte migration. Evaluation of CXCR4, the SDF1alpha receptor, revealed reduced expression of surface CXCR4 on GD-derived monocytes, despite similar CXCR4 mRNA transcript levels in the monocytes of healthy volunteers and GD patients. Reduction of surface CXCR4 was accompanied by increased intracellular CXCR4 levels in patient monocytes. This elevated intracellular CXCR4 might reflect significantly increased SDF1alpha concentrations characterizing patients' serum and the lysosomal impairment of GD, resulting in decreased degradation of CXCR4. Different distributions of CXCR4 expression observed in the two groups explain impaired SDF1alpha-dependent monocyte migration. Reduced numbers and impaired migration capacity of GD-derived monocytes could contribute to abnormal inflammation and GD-associated immune alterations seen in these patients.

Authors: Bettman N, Avivi I, Rosenbaum H, Bisharat L, Katz T
Journal: Blood Cells Mol. Dis.; 2015 Aug; 55(2) 180-6. doi:10.1016/j.bcmd.2014.12.003
Year: 2015
PubMed: PMID: 25564295 (Go to PubMed)