Cell Surface CD36 Protein in Monocyte/Macrophage Contributes to Phagocytosis during the Resolution Phase of Ischemic Stroke in Mice

Infiltrating monocyte-derived macrophages (M-M-phi) influence stroke-induced brain injury. Although the inflammatory nature of M-M-phi in acute stroke has been well documented, their role during the resolution phase of stroke is less clear. With emerging evidence for the involvement of scavenger receptors in innate immunity, this study addresses an M-M-phi CD36 role in mediating phagocytosis during the recovery phase of stroke. Stroke increases CD36 and TSP-1/2 mRNA levels in the ipsilateral hemisphere at acute (3-day (d)) and recovery (7d) periods. Quantification of total, intracellular, and cell surface CD36 protein levels showed relatively unchanged expression at 3d post-ischemia. At 7d, there was a significant increase in cell surface CD36 (p < 0.05) with a concurrent reduction of intracellular CD36 (p < 0.05) in the ipsilateral hemisphere. Both cell surface and intracellular CD36 were found in whole brain lysates, whereas cell surface CD36 was predominantly detected in isolated brain mononuclear cells, blood monocytes, and peritoneal macrophages, suggesting that cell surface CD36 expressed in the post-ischemic brain originates from the periphery. The stroke-induced CD36 mRNA level correlated with increased expression of lysosomal acid lipase, an M2 macrophage marker. Functionally, higher CD36 expression in M-M-phi is correlated with higher phagocytic indices in post-ischemic brain immune cells. Moreover, pharmacological inhibition of CD36 attenuated phagocytosis in peritoneal macrophages and brain M-M-phi. These findings demonstrate that cell surface CD36 on M-M-phi mediates phagocytosis during the recovery phase in post-stroke brains and suggests that CD36 plays a reparative role during the resolution of inflammation in ischemic stroke.