Figure 5.

CSF3 is produced by cerebral endothelial cells in a CD36-dependent manner and increases neutrophil ROS and ischemic injury in CD36-null hosts receiving WT BM. A, Cxcl1, Cxcl2, and Csf3 mRNA is upregulated in primary mouse brain endothelial cell (MBEC) cultures exposed for 6 h to brain extracts from ischemic tissue (Ipsi, ipsilateral hemisphere) but when exposed to brain extract from nonischemic tissue (Sham surgery or Contra, contralateral hemisphere). Reduced production of Csf3 is observed in CD36 KO EC cultures exposed to ischemic brain extract (n = 6/group). *p < 0.05 versus WT. B, Intracerebroventricular administration of CSF3 (1 μg) 24 h after MCAo increases ischemic brain injury in CD36 KO mice receiving WT bone marrow (WT BM→KO Host), whereas CSF3 administration does not affect the injury in WT mice receiving WT marrow (WT BM→WT Host) (n = 9–11 mice/group). *p < 0.05 versus vehicle. C, CSF3-mediated reconstitution of ischemic brain injury is accompanied by an increase in the number of neutrophils producing ROS in WT BM→KO Host chimeras (n = 4 mice/group). *p < 0.05 versus vehicle. Values are mean ± SE.