Downregulation 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) epitope of bovine cartilage proteoglycan stains ramified microglia in the rat brain. In this study we show that 5D4-positive microglia is abundant in the normal rat spinal cord and nearly absent during both the active and recovery phase of experimental autoimmune encephalomyelitis (EAE) in myelin-immunized Lewis rats. In contrast, during Wallerian degeneration of the optic nerve the density of KS-immunoreactive microglia remains constant. KS immunoreactivity is absent from both normal and transected sciatic nerves, and spinal nerve roots. On immunoblots of spinal cord extracts MAb 5D4 stains a novel type of KS proteoglycans (KSPGs) 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 nervous systems and may partially account for the rapid macrophage response to axonal injury in the peripheral nervous system. Downregulation of microglial KSPG could be a prerequisite for a rapid inflammatory response in the central nervous system.
Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany.
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Jander
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Stoll
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D015536:Down-Regulation; D004679:Encephalomyelitis / Q000378:metabolism*; D005260:Female; D007632:Keratan Sulfate / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014855:Wallerian Degeneration / Q000502:physiology*
D007632:Keratan Sulfate