Journal: Biochemical and biophysical research communications

Article Title: NLRP3 inflammasome-mediated platelet hyperreactivity in sickle cell mice is targetable by BTK inhibition

doi: 10.1016/j.bbrc.2026.153355

Figure Lengend Snippet: (A, B) Compared with vehicle, treatment of mice with the BTK inhibitor ibrutinib decreases ASC (red)-NLRP3 (green) colocalization in collagen-activated platelets from SS mice but not AA mice, with a significant treatment-by-genotype interaction (p = 0.0011). Scale bar, 1 μm. In SS mice, ibrutinib decreases platelet P-selectin expression (C), ATP secretion (D), spreading (E, F), aggregation (G), and in vitro thrombus formation (H). In AA mice, ibrutinib reduces ATP secretion (D) and aggregation (G) only. Significant treatment-by-genotype interactions were observed for ATP secretion (D), platelet spreading (E, F), aggregation (G), and thrombus formation (H) (p < 0.0001, p < 0.0001, p = 0.0009, p = 0.0373, respectively). The NLRP3 activator nigericin partially reverses the inhibitory effects of ibrutinib in samples from ibrutinib-treated SS (C–H) and AA mice (C, D, G). Nigericin has no effect on samples from vehicle-treated SS mice (C–H) but increases platelet p-selectin expression (C), platelet ATP secretion (D), platelet aggregation (G), and in vitro thrombus formation (H) in samples from vehicle-treated AA mice. Significant 3-way interactions among genotype, ibrutinib, and nigericin were observed for platelet P-selectin expression (C) and ATP secretion (D) (p = 0.0094 and p = 0.0321, respectively). Data are shown as scatter dot plots with mean ± SD. N = 4–6 mice per group. *p < 0.05, **p < 0.01, ***p < 0.001.

Article Snippet: Mice received IV injections of the NLRP3 inhibitor MCC950 (Cayman Chemical, 50 mg/kg) or the BTK inhibitor ibrutinib (Selleckchem, 10 mg/kg) 4 h prior to blood collection by cardiac puncture into heparinized syringes.

Techniques: Expressing, In Vitro