DOWN-REGULATION OF MICROGLIAL KERATAN SULFATE PROTEOGLYCANS COINCIDENT WITH LYMPHOMONOCYTIC INFILTRATION OF THE RAT CENTRAL-NERVOUS-SYSTEM

The monoclonal antibody (MAb) 5D4 against a keratan sulfate (KS) epito pe of bovine cartilage proteoglycan stains ramified microglia in the r at brain. In this study we show that 5D4-positive microglia is abundan t in the normal rat spinal cord and nearly absent during both the acti ve and recovery phase of experimental autoimmune encephalomyelitis (EA E) in myelin-immunized Lewis rats. In contrast, during Wallerian degen eration of the optic nerve the density of KS-immunoreactive microglia remains constant. KS immunoreactivity is absent from both normal and t ransected sciatic nerves, and spinal nerve roots. On immunoblots of sp inal cord extracts MAb 5D4 stains a novel type of KS proteoglycans (KS PGs) with an apparent molecular weight mainly between 140 and 200 kd, which significantly decrease in acute EAE. Our data suggest that high levels of KSPG expression correlate to a downregulated immunophenotype of resident macrophages in the nervous system. The lack of detectable KS in peripheral nerve points to a divergent differentiation of bone marrow-derived resident macrophages in the peripheral and central nerv ous systems and may partially account for the rapid macrophage respons e to axonal injury in the peripheral nervous system. Downregulation of microglial KSPG could be a prerequisite for a rapid inflammatory resp onse in the central nervous system.