Abstract TMP68: A Pro-inflammatory Monocyte Subset (ccr2+/ly6chi) Is Dominantly Recruited Into Acute Ischemic Brain.
Post-ischemic inflammation has been associated with ischemic brain injury. Infiltrated peripheral immune cells including monocytes/macrophages (MMs) contribute to the stroke-induced inflammation. MM mobilization from the periphery to the brain (MM trafficking) involves spleen, as an immediate storage of monocytes and the circulatory system as a conduit for their transport; however, there has been no systematic analysis of MM trafficking in stroke. There are two monocyte subsets, a pro-inflammatory (CCR2+/Ly6Chi) and an anti-inflammatory (CCR2-/Ly6Clo). These are sequentially recruited to the injury site in a controlled manner to elicit inflammation and repair/healing respectively. Current study determines the extent of trafficking of the monocyte subsets upon stroke and the role of the subsets on stroke-induced brain injury. Eleven week-old C57BL mice were subjected to transient middle cerebral artery occlusion and then leukocytes were isolated from blood, spleen, and brain prior to, 1d-, and 3d-post ischemia. The cells were incubated with antibodies (lineage marker or CD45 and CD11b to detect MMs, and Ly6C) and then analyzed using flow cytometry/FACS. We observed decreased spleen size following ischemia (>40% reduction in spleen weight at 1d- and 3d-post). Both Ly6Chi and Ly6Clo MM number in the spleen and blood were significantly decreased in 1d-post ischemic mice, and these levels were sustained until 3d-post ischemia. On the other hand, brain MM numbers were increased at 1d-post and further increased at 3d-post ischemia (Fig. 1). Importantly, the Ly6Chi subset was dominantly increased in the ischemic brain compared to Ly6Clo subset (Fig. 2). The findings of MM trafficking and predominant increase in Ly6Chi MMs in the ischemic brain indicate that the pro-inflammatory monocyte subset might have a critical role in acute ischemic brain injury. Selective targeting of pro-inflammatory subset is suggested to reduce acute stroke-induced brain injury.
- © 2012 by American Heart Association, Inc.