Circulating PMos engulf sickle RBCs in SCD. (A) Representative dot plots comparing GPA⁺ (an RBC marker) CMos (CD45⁺HLA-DR⁺SSC^hiCD14^hiCD16⁻) and PMos (CD45⁺HLA-DR⁺SSC^hiCD14^lowCD16⁺) from race-matched HDs and patients with SCD. For the gating strategy used, see supplemental Figure 4A. (B) Frequencies of GPA⁺ circulating monocyte populations in HDs (n = 17), patients with SCD at steady state (n = 17), and during acute crisis (n = 11). (C) Representative IFC images acquired simultaneously and gated on GPA⁺ PMos from patients with SCD (from A). Left to right: single-channel bright field (BF), CD45 (representing PMos in purple), GPA (representing RBC materials in green), and merged images showing GPA⁺ materials within CD45⁺ cells in the top 4 rows, but not in the bottom row, where GPA⁺ material is attached to the external surface of PMos. (D) Histogram depicting degree of GPA⁺ material internalized within PMos with internalization score (<0 represents GPA⁺ material attached to the surface of PMos; >0 represents GPA⁺ material internalized by PMos). Percentage of cells with an internalization score >0 is indicated. (E) Frequency of PMos within total circulating monocytes from HD (n = 10), patients with SCD at steady state (n = 17), and during acute crisis (n = 11) were determined by FCM. Data represent mean ± SEM; means were compared using a 2-tailed Student t test. **P < .01; ***P < .001.