Mast cell activation contributes to neuro-inflammation in SCA. (A-K) HbSS-BERK mice were treated with saline (Veh), CS, or imatinib mesylate (Imat) for 5 days followed by analysis as indicated with each figure. (A) Representative images of Toluidine blue–stained dorsal skin sections. n = 6; bar = 100 μm. (B) Ratio of degranulating/total mast cells. *P < .01 vs HbAA-BERK, #P < .05 vs HbSS-BERK Veh (ANOVA, with Bonferroni). (C-D) Levels of tryptase, β-hexosaminidase (β-hex), SAP, SP, and CGRP expressed as the percentage of HbAA-BERK values. Red bars, HbSS-veh; magenta bars, HbSS-CS; blue bars, HbSS-Imat. *P < .05, **P < .01 vs HbAA-BERK, #P < .05, ##P < .01 vs HbSS-BERK Veh (ANOVA, with Bonferroni). (E-F) Cytokine released following 24 hours of incubation of skin from mice treated with vehicle or imatinib for 5 days. Black bars, HbAA-BERK Veh; red bars, HbSS-BERK Veh; blue bars, HbSS-BERK imatinib. Values are expressed as a percent of HbAA (E) or HbSS veh (F). *P < .05, **P < .01 vs HbAA-BERK Veh (E) or HbSS-BERK Veh (F) (Student t test). (G) Linear regression analysis of the expression of plasma GM-CSF and total WBC counts. (H-K) Neuropeptide release from the skin (H-I) and DRG (J-K) following 24 hours in culture. *P < .05, **P < .01 vs HbAA-BERK (H,J). *P < .05 vs HbSS-BERK Veh, **P < .01 vs HbSS-BERK Veh (I,K) (ANOVA, with Bonferroni). Each value is the mean ± SEM of 6 mice per group (in B-K). (L) Percentage of degranulating mast cells in DRG of mice treated with vehicle or imatinib for 5 days. *P < .001 vs HbAA-BERK Veh, #P < .05 vs HbSS-BERK Veh (ANOVA, with Bonferroni). (M-N) Representative confocal images showing coexpression of ATF3 (green) and GFAP (red). Scale bar, 100 µm; n = 6.