Extended Data Fig. 9: Extended Data Fig. 9.
a, Hematology assessment demonstrate that SWNT-SHP1i treatment results in a significant decrease in the mean platelet volume (MPV) and platelet-large cell ratio (P-LCR), but has no effect on major parameters of the complete blood count or metabolic panel that would indicate organ or hematopoietic toxicity (n = minimum 9 biologically independent animals per group). *p < 0.05 by unpaired two-tailed t-test. b-d, In contrast to prior publications indicating that global knockout of SHP-1 can have a variety of harmful effects including dermatitis, pneumonitis, and renal complement deposition (images adapted from Supplementary refs. 3,4,5), we observed none of these toxicities in mice treated with macrophage-specific SWNT-SHP1i6. This favorable safety profile was evidenced by a lack of hair loss or suppurative skin lesions (b), an absence of pulmonary inflammation and alveolar hemorrhage (c), and the absence of elevated renal C3 immunofluorescence staining (n = 5 per group, 4 sections analyzed per animal) (d). Scale bar in c, 100μm. Scale bars in d, 200 μm and 50 μm (insets). SHP1-deficient image in 9c reprinted with permission from Supplementary ref. 4; Copyright (2008) National Academy of Sciences, U.S.A. For all graphs, data are expressed as the mean and s.e.m.
