Figure 3
From: Hypoxia-mediated impaired erythrocyte Lands’ Cycle is pathogenic for sickle cell disease
shRNA specific knockdown of cPLA2 in HSCs of BMT SCD chimeras attenuated sickling, hemolysis and inflammation.
(a) Schematic flow of mouse treatment strategy and experimental procedure. (b–f) PLA2 activity (b), LysoPC content (c), PC content (d), the ratio of LysoPC/PC (e) and the percentage of LysoPC/PL (f) were quantified in the erythrocytes from SCD chimeras mice with scrambled shRNA or cPLA2 shRNA. Error bars, SEM; n = 5–7 per group. (g) Circulating AA was significantly decreased in SCD chimeras with specific cPLA2 knockdown. (h) Percentages of sickled cells and reticulocytes were significantly reduced in the SCD chimeras with HSC-specific cPLA2 knockdown. (i–l) cPLA2 knockdown in HSCs of BMT SCD chimeras decreased plasma hemoglobin levels (i), leukotriene B4 (j), prostaglandin E2 (k) and reduced circulating IL-6 (l). Values shown represent the mean ± SEM (n = 5–7). (m) H&E staining of spleens, livers and lungs of SCD chimeras with HSC-specific cPLA2 knockdown and controls. *P < 0.05 versus SCD chimeras with BMCs infected with recombinant lentivirus encoding scrambled shRNA.
