Abstract TP266: Infiltrated CD36+ Monocytes/Macrophages are the Main Phagocytes in Acute Ischemic Stroke

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Abstract

Introduction: Stroke induces the infiltration of peripheral monocytes/macrophages [MMs] into the injured brain. As MMs share common lineage markers with resident microglia [Mig], defining their respective phenotypes and function has been a challenge. CD36, a multifunctional receptor, is expressed in mononuclear cells and microvasculature. Besides its involvement in stroke-induced inflammation, CD36 also functions in innate immunity by phagocytizing debris and apoptotic cells.

Hypothesis: We hypothesized that infiltrated CD36+ MMs in the ischemic brain are major phagocytes.

Methods: Adult Male C57 mice were subjected to a 30-min transient focal ischemia. Peripheral MM trafficking to ischemic brain was determined by adoptive transfer of GFP+-splenocytes 1 day (D) prior to sacrifice. Isolated brain immune cells at 3 or 7D post-stroke were analyzed by a flow cytometer (CD11b/CD45/CD36). Phagocytosis assay was performed using fluorescent bead in the absence /presence of salvianolic acid B (SAB), a CD36 inhibitor.

Results: In CD11b+ cells, CD45Low was present in both hemispheres while CD45High was exclusively found in stroked hemisphere. The number of ipsilateral CD36+ cells was higher in CD45High than CD45Low subset (315±254 vs 46±38, n=7, p<0.01). Infiltrated GFP+ cells mostly belong to CD45High. Phagocytic activity measured in the brain immune cells at 7D post-stroke was positively correlated with CD36 expression (Fig), which was attenuated by SAB treatment (98±17 vs 75±8, n=5, p<0.05).

Conclusion: The results show that CD45High subset represents infiltrated MMs and infiltrated CD36+ MMs are the main phagocytes in the post-stroke brain. With previously reported CD36 role in post-stroke inflammation, CD36-mediated phagocytosis in MMs provides further insights on the dichotomy of CD36 function in inflammation and subsequent resolution of post-stroke inflammation.

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