Can a macrophage differentiate back into a monocyte? I know that monocytes differentiate into macrophages when they enter the tissues, but do macrophages stay in those same tissues for the remainder of their lifespan, or do they differentiate back into monocytes and re-enter the bloodstream at some point?

No, macrophages can not turn back into monocytes, usually once a monocyte travels around the bloodstream for 1-3 days, it then leaves the bloodstream and travel to a tissue where it will differentiate to a macrophage or dendritic cell. It undergoes a conformational change, this usually happens during inflammation as the macrophages travel over a chemical gradient, macrophages can still enter the bloodstream, however, they won't re-differentiate to a monocyte. So to answer your question directly, macrophages don't stay in the same tissue forever as their life span is pretty long(1-2 months) so most likely an inflammation will occur and force the macrophages to diffuse across the chemical gradient, but they usually patrol around the tissue area where they differentiated.

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