The scavenger receptor CD36 contributes to the neurotoxicity of bone marrow-derived monocytes through peroxynitrite production.

摘要: Abstract CD36, a class B scavenger receptor present in microglia, endothelium and leukocytes, plays key role ischemic brain injury by promoting the expression of inflammatory genes production reactive oxygen species (ROS). However, it is not known whether damage mediated CD36 activation resident cells, i.e., or blood-borne cells that infiltrate brain. To address this question, we studied oxygen–glucose deprivation (OGD) hippocampal slice cultures, model does involve extrinsic to We found gene knockout afford protection slices OGD-induced cytotoxicity. In contrast, immunoactivated bone marrow-derived monocytes–macrophages (BMM) from wild type (WT) mice trigger when incubated with via mechanism prevented CD36−/− BMM. The neurotoxic activity CD36+/+ BMM was attributed (ROS) since concomitant increased ROS could be treatment selective scavenger, MnTBAP, peroxynitrite decomposition catalyst, FeTPPS. Importantly, accumulation 3-nitrotyrosine proteins (a hallmark production) significantly dampened BMM, whereas NO-derived metabolites (nitrite nitrate) unaltered. conclude signaling may contribute induced OGD itself but involved neurotoxicity activated These findings are consistent hypothesis infiltrating drives peroxynitrite-mediated damage. Accordingly, targeting vascular compartment protect against