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MΦ-mediated BM failure
Monocytes (CD11b+ Ly6Chi) and Mfs (defined as CD11blo/– Mfs: F4/80+ VCAM1+ CD169+ CD11blo/– SSClo and CD11b+ Mfs: F4/80+ VCAM1+ CD169+ CD11b+Ly6Cint SSClo; Online Supplementary Figure S2), were increased by frequency 8 d.p.s.t., relative to Rad mice (Figure 1C). At 15
sist despite SAA-associated cytopenias, myeloid cell loss, and HSC loss in SAA. These data suggest that CD11blo/– Mfs do not require hematopoietic input during SAA, potentially due to their long lifespan or ability to self- renew.
+
d.p.s.t., CD11b Mfs, monocytes, and neutrophils were
IFNγ-dependent increase in BM macrophages during SAA drives HSC loss and thrombocytopenia
lo/-
reduced by frequency whereas CD11b Mf frequencies
were significantly increased (Figure 1D). Despite severe BM hypocellularity at 15 d.p.s.t., CD11blo/– Mf numbers remained stable (Figure 1F). Thus, BM CD11blo/– Mfs per-
AB
Interferon-γ mediates SAA pathology5,9 and maintains BM Mfs during infection,21 thus we next addressed
CD
Figure. 1. Bone marrow (BM) macrophages are main- tained during aplastic anemia. (A and B) Hematoxylin and eosin-stained BM in radiation control (Rad) (top) and severe aplastic anemia (SAA) (bottom) mice on days 8 and 15. Scale bar=100μm. Frequencies (C and D) and numbers (E and F) of CD11blo/- Mfs, CD11b+ Mfs, monocytes, and neutrophils in radiation control (open bars) and SAA (filled bars) mice on days 8 and 15. Data represent one experiment repeated at least twice, n=3-6 mice/group. Mean±Standard Error of Mean is shown. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.
haematologica | 2018; 103(9)
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