ED2-positive perivascular phagocytes produce interleukin-1beta during delayed neuronal loss in the facial nucleus of the rat.

Injection of Fluoro-Gold (FG) into the whisker pad of rats yields stable retrograde labeling of facial motoneurons. Subsequent removal of 10 mm from all facial nerve branches permanently deprives the FG-labeled motoneurons from their targets and the motoneurons gradually die. Neuronal debris is phagocytized by two types of neuronophages: parenchymal microglia (monoclonal antibody [MAb] OX42-positive, MAb ED2-negative) and perivascular phagocytes (OX42-negative, ED2-positive). Because both types of neuronophages express major histocompatibility complex (MHC) class II glycoproteins (MAb OX6-positive), they are considered to be the potential antigen-presenting cells of the brain. To check this hypothesis, we tested whether both types of neuronophages also synthetize the co-stimulatory cytokine interleukin-1beta (IL-1beta) immunocytochemically visualized by MAbs SILK-5/6. Employing combined fluorescent visualization of antigens (OX6, ED2, and SILK-5/6) in sections containing fluorescent (FG-prelabeled) neuronophages, we found that, during slowly occurring neuronal loss, the vast majority of IL-1beta immunoreactive neuronophages were of perivascular (ED2-positive) origin. We concluded that, during delayed neuronal death "behind" an intact blood-brain barrier, the perivascular phagocytes were more likely to function as antigen-presenting cells than the parenchymal microglia.