title: Cell Surface CD36 Protein in Monocyte/Macrophage Contributes to Phagocytosis during the Resolution Phase of Ischemic Stroke in Mice.
abstract: Infiltrating monocyte-derived macrophages (M-MΦ) influence stroke-induced brain injury. Although the inflammatory nature of M-MΦin 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-MΦCD36 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-MΦis correlated with higher phagocytic indices in post-ischemic brain immune cells. Moreover, pharmacological inhibition of CD36 attenuated phagocytosis in peritoneal macrophages and brain M-MΦThese findings demonstrate that cell surface CD36 on M-MΦmediates 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.
authors.affiliation: From the Burke-Cornell Medical Research Institute, White Plains, New York 10605 and the Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10065.
authors.forename: Moon-Sook
authors.initials: MS
authors.lastname: Woo
authors.affiliation: From the Burke-Cornell Medical Research Institute, White Plains, New York 10605 and the Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10065.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Yang
authors.affiliation: From the Burke-Cornell Medical Research Institute, White Plains, New York 10605 and the Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10065.
authors.forename: Cesar
authors.initials: C
authors.lastname: Beltran
authors.affiliation: From the Burke-Cornell Medical Research Institute, White Plains, New York 10605 and the Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10065 suc2002@med.cornell.edu.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Cho
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018955:CD36 Antigens / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics; D020521:Stroke / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D018955:CD36 Antigens; D012333:RNA, Messenger
keywords: CD36; inflammation; ischemic stroke; macrophage; monocyte; phagocytosis; resolution; stroke